Parasites, Hosts and Diseases

"Guang-Ho Cha"

Original Articles

Anti-tumor effects of Toxoplasma gondii and antigen-pulsed dendritic cells in mice bearing breast cancer: Bong Kyun Kim, Hei Gwon Choi, Jae-Hyung Lee, In Wook Choi, Jae-Min Yuk, Guang-Ho Cha, Young-Ha Lee; Parasites Hosts Dis 2025;63(1):37-49.
Published online February 25, 2025; DOI: https://doi.org/10.3347/PHD.24082

Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8⁺ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8⁺ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.

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Detection of Toxoplasma gondii and High-Risk Human Papillomaviruses in FFPE Malignant and Benign Breast Lesions Using Real-Time PCR
Selma Usluca, Ayfer Bakir, Ata Arikok, Gizem Korkut, Gulsah Yagiz, Murat Alper
Infection and Drug Resistance.2025; Volume 18: 3149. CrossRef

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Probiotic-induced changes in intestinal microbiome inhibits Toxoplasma gondii infection: Hak-Jae Lee, Do-Won Ham, Seung-Hwan Seo, Guang-Ho Cha, Eun-Hee Shin; Parasites Hosts Dis 2024;62(4):408-423.
Published online November 22, 2024; DOI: https://doi.org/10.3347/PHD.24068

Abstract
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Toxoplasma gondii primarily invades the central nervous system, causing latent infections. Cysts persist in the host for life and there is currently no effective treatment. T. gondii infects human hosts through contaminated meat, invading the intestinal tissue and leading to changes in the number and composition of the gut microbiota. Since probiotic ingestion modulates intestinal microbiota changes, we hypothesized that intestinal microbiota dysbiosis caused by T. gondii infection would be restored following probiotic supplementation. To this end, we orally infected C57BL/6 mice with 10 T. gondii cysts and administered supplemental probiotics daily. We analyzed the levels of T. gondii B1 gene DNA, indicative of T. gondii infection, in brain tissue. We investigated alterations in the gut microbiota composition and functional pathways between the probiotic and non-probiotic treatment groups via next-generation sequencing analysis of each fecal sample. The infection level in the probiotic-treated group was significantly reduced after 4 weeks (p<0.05). Probiotic supplementation notably changed the gut microbiota after 2 weeks of infection, increasing the relative abundance of Intestinimonas massiliensis and Lawsonibacter asaccharolyticus. Probiotic supplements appear to modulate the gut microbiota, activating functional pathways involved in intestinal short-chain fatty acid production and strengthening the intestinal barrier, thereby impeding T. gondii infection and subsequent proliferation. Our findings provide valuable insights into T. gondii infection control and future study directions.

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Lactobacillus vaginalis alleviates DSS induced colitis by regulating the gut microbiota and increasing the production of 3-indoleacrylic acid
Zhuoya Wang, Tian Liu, Li Liu, Jian Xie, Furui Tang, Yimin Pi, Yuchun Zhong, Zhidong He, Wenming Zhang, Cihua Zheng
Pharmacological Research.2025; 213: 107663. CrossRef
Gut microbiota-derived butyrate alleviates the impairment of mice intestinal integrity caused by Toxoplasma gondii infection
Shuni Liu, Yutao Zheng, Bingqian Cui, Jiayi Yang, Bohui Yuan, Yuhan Cao, Zimu Zhao, Zhuo Sun, Qingling Wang, Xiaoying Yang, Wei Pan, Cheng He
Life Sciences.2025; 374: 123709. CrossRef
Analysis of Gut Microbiota and Assessment of Environmental Health in Western Anatolian Vole (Microtus lydius Blackler, 1916)
Tuba Yağcı, Gözde Ayseçkin
Journal of Anatolian Environmental and Animal Sciences.2025; 10(4): 471. CrossRef
Microbiome of Dipteran vectors associated with integron and antibiotic resistance genes in South Korea
Xavier Chavarria, Arwa Shatta, Hyun Seo Park, Du-Yeol Choi, Dongjun Kang, Singeun Oh, Dawon Lee, Myungjun Kim, Jun Ho Choi, Yoon Hee Cho, Myung-hee Yi, Ju Yeong Kim
Acta Tropica.2025; 271: 107858. CrossRef
Urban environmental drivers of eukaryotic microbiota and parasite prevalence in domestic pigeon faeces: a metabarcoding-based public health risk assessment in Seoul, South Korea
Singeun Oh, Jun Ho Choi, Xavier Chavarria, Myungjun Kim, Dongjun Kang, Myung-hee Yi, Yoon Hee Cho, In-Yong Lee, Tai-Soon Yong, Seongjun Choe, Ju Yeong Kim
Journal of The Royal Society Interface.2025;[Epub] CrossRef

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Expression of cytokines and co-stimulatory molecules in the Toxoplasma gondii-infected dendritic cells of C57BL/6 and BALB/c mice: Jae-Hyung Lee, Jae-Min Yuk, Guang-Ho Cha, Young-Ha Lee; Parasites Hosts Dis 2023;61(2):138-146.
Published online May 23, 2023; DOI: https://doi.org/10.3347/PHD.22150

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1β, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1β was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

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Anti-tumor effects of Toxoplasma gondii and antigen-pulsed dendritic cells in mice bearing breast cancer
Bong Kyun Kim, Hei Gwon Choi, Jae-Hyung Lee, In Wook Choi, Jae-Min Yuk, Guang-Ho Cha, Young-Ha Lee
Parasites, Hosts and Diseases.2025; 63(1): 37. CrossRef
Influenza virus-like particles presenting Toxoplasma gondii dense granule protein 7 protect mice from lethal ME49 challenge
Jie Mao, Hae-Ji Kang, Su-In Heo, Fu-Shi Quan
Nanomedicine.2025; 20(18): 2309. CrossRef
Toxoplasma gondii IST suppresses inflammatory and apoptotic responses by inhibiting STAT1-mediated signaling in IFN-γ/TNF-α-stimulated hepatocytes
Seung-Hwan Seo, Ji-Eun Lee, Do-Won Ham, Eun-Hee Shin
Parasites, Hosts and Diseases.2024; 62(1): 30. CrossRef
Contrasting Disease Progression, Microglia Reactivity, Tolerance, and Resistance to Toxoplasma gondii Infection in Two Mouse Strains
Daniel G. Diniz, Jhonnathan H. P. de Oliveira, Luma C. F. Guerreiro, Gabriel C. de Menezes, Alexa C. L. de Assis, Tainá Q. Duarte, Izabelly B. D. dos Santos, Flávia D. Maciel, Gabrielly L. da S. Soares, Sanderson C. Araújo, Felipe T. de C. Franco, Ediclei
Biomedicines.2024; 12(7): 1420. CrossRef
Recombinant SAG2A Protein from Toxoplasma gondii Modulates Immune Profile and Induces Metabolic Changes Associated with Reduced Tachyzoite Infection in Peritoneal Exudate Cells from Susceptible C57BL/6 Mice
Thaíse Anne Rocha dos Santos, Mário Cézar de Oliveira, Edson Mario de Andrade Silva, Uener Ribeiro dos Santos, Monaliza Macêdo Ferreira, Ana Luísa Corrêa Soares, Neide Maria Silva, Tiago Antônio de Oliveira Mendes, Jamilly Azevedo Leal-Sena, Jair Pereira
Microorganisms.2024; 12(11): 2366. CrossRef

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The Role of PI3K/AKT Pathway and NADPH Oxidase 4 in Host ROS Manipulation by Toxoplasma gondii: Hei Gwon Choi, Fei-Fei Gao, Wei Zhou, Pu-Reum Sun, Jae-Min Yuk, Young-Ha Lee, Guang-Ho Cha; Korean J Parasitol 2020;58(3):237-247.
Published online June 26, 2020; DOI: https://doi.org/10.3347/kjp.2020.58.3.237

Abstract
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Dendritic cell is one of the first innate immune cell to encounter T. gondii after the parasite crosses the host intestinal epithelium. T. gondii requires intact DC as a carrier to infiltrate into host central nervous system (CNS) without being detected or eliminated by host defense system. The mechanism by which T. gondii avoids innate immune defense of host cell, especially in the dendritic cell is unknown. Therefore, we examined the role of host PI3K/AKT signaling pathway activation by T. gondii in dendritic cell. T. gondii infection or T. gondii excretory/secretory antigen (TgESA) treatment to the murine dendritic cell line DC2.4 induced AKT phosphorylation, and treatment of PI3K inhibitors effectively suppressed the T. gondii proliferation but had no effect on infection rate or invasion rate. Furthermore, it is found that T. gondii or TgESA can reduce H₂O₂-induced intracellular reactive oxygen species (ROS) as well as host endogenous ROS via PI3K/AKT pathway activation. While searching for the main source of the ROS, we found that NADPH oxidase 4 (NOX4) expression was controlled by T. gondii infection or TgESA treatment, which is in correlation with previous observation of the ROS reduction by identical treatments. These findings suggest that the manipulation of the host PI3K/AKT signaling pathway and NOX4 expression is an essential mechanism for the down-regulation of ROS, and therefore, for the survival and the proliferation of T. gondii.

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Small molecule kinase inhibitor altiratinib inhibits brain cyst forming bradyzoites of Toxoplasma gondii
Yeong Hoon Kim, Hye-Jin Ahn, Hwa Sun Kim, Ho-Woo Nam
Journal of Microbiology.2025; 63(2): e2409001. CrossRef
The role of Nrf2 signaling in parasitic diseases and its therapeutic potential
Mohammadamin Vatankhah, Reza Panahizadeh, Ali Safari, Alireza Ziyabakhsh, Behnam Mohammadi-Ghalehbin, Narges Soozangar, Farhad Jeddi
Heliyon.2024; 10(12): e32459. CrossRef
Brain –cyst-driven genes expression in Toxoplasma Gondii Tehran strain: a parasitic-immunogenicity assessment by dint of RNA-Seq
Marzieh Asadi, Zahra Babaei, Ali Afgar, Mohammad Hossein Banabazi, Naser ZiaAli, Ahmad Daryani, Ehsan Aghajani, Milad Mahdavi, Mohamadreza Attari, Farzaneh Zarrinkar
Veterinary Research Communications.2024; 48(4): 2563. CrossRef
BjussuLAAO-II, an l-amino acid oxidase from Bothrops jararacussu snake venom, impairs Toxoplasma gondii infection in human trophoblast cells and villous explants from the third trimester of pregnancy
Thales Alves de Melo Fernandes, Samuel Cota Teixeira, Tássia Rafaela Costa, Alessandra Monteiro Rosini, Guilherme de Souza, Lorena Polloni, Bellisa de Freitas Barbosa, Marcelo José Barbosa Silva, Eloisa Amália Vieira Ferro, Veridiana de Melo Rodrigues Ávi
Microbes and Infection.2023; 25(6): 105123. CrossRef
Toxoplasma gondii inhibits the expression of autophagy-related genes through AKT-dependent inactivation of the transcription factor FOXO3a
Andres Felipe Diez, Louis-Philippe Leroux, Sophie Chagneau, Alexandra Plouffe, Mackenzie Gold, Visnu Chaparro, Maritza Jaramillo, Anita A. Koshy
mBio.2023;[Epub] CrossRef
Regulation of phosphoinositide metabolism in Apicomplexan parasites
Angela Arabiotorre, Vytas A. Bankaitis, Aby Grabon
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth
Fei‐Fei Gao, Juan‐Hua Quan, In‐Wook Choi, Yeon‐Jae Lee, Seul‐Gi Jang, Jae‐Min Yuk, Young‐Ha Lee, Guang‐Ho Cha
Journal of Cellular and Molecular Medicine.2021; 25(19): 9460. CrossRef

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Dipenyleneiodonium Induces Growth Inhibition of Toxoplasma gondii through ROS Induction in ARPE-19 Cells: Pu Reum Sun, Fei Fei Gao, Hei Gwon Choi, Wei Zhou, Jae-Min Yuk, Jaeyul Kwon, Young-Ha Lee, Guang-Ho Cha; Korean J Parasitol 2019;57(2):83-92.
Published online April 30, 2019; DOI: https://doi.org/10.3347/kjp.2019.57.2.83

Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investigated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the intracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, followed by suppression of T. gondii infection and proliferation. The involvement of ROS in anti-parasitic effect of DPI was confirmed by finding that DPI effect on T. gondii can be reversed by ROS scavengers, N-acetyl-L-cysteine and ascorbic acid. These results suggest that, in ARPE-19 cell, DPI can enhance host ROS generation to prevent T. gondii growth. Our study showed DPI is capable of suppressing T. gondii growth in host cells while minimizing the un-favorite side-effect to host cell. These results imply that DPI as a promising candidate material for novel drug development that can ameliorate toxoplasmosis based on ROS regulation.

Citations

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Small molecule kinase inhibitor altiratinib inhibits brain cyst forming bradyzoites of Toxoplasma gondii
Yeong Hoon Kim, Hye-Jin Ahn, Hwa Sun Kim, Ho-Woo Nam
Journal of Microbiology.2025; 63(2): e2409001. CrossRef
MjTX-II, a Lys49-PLA2 from Bothrops moojeni snake venom, restricts Toxoplasma gondii infection via ROS and VEGF regulation
Samuel Cota Teixeira, Thales Alves de Melo Fernandes, Guilherme de Souza, Alessandra Monteiro Rosini, Aryani Felixa Fajardo Martínez, Angelica Oliveira Gomes, Rosiane Nascimento Alves, Daiana Silva Lopes, Maria Vitoria da Silva, Emidio Beraldo-Neto, Patrí
Chemico-Biological Interactions.2025; 409: 111417. CrossRef
High-Throughput Repurposing Screen Reveals Compounds with Activity against Toxoplasma gondii Bradyzoites
Taher Uddin, Jing Xia, Yong Fu, Case W. McNamara, Arnab K. Chatterjee, L. David Sibley
ACS Infectious Diseases.2025; 11(3): 600. CrossRef
In Vitro Inhibitory Activity of Corilagin and Punicalagin Against Toxoplasma gondii and Their Mechanism(s) of Action
Nicole T. Green-Ross, Homa Nath Sharma, Audrey Napier, Boakai K. Robertson, Robert L. Green, Daniel A. Abugri
Antibiotics.2025; 14(4): 336. CrossRef
Metabolic changes in Toxoplasma gondii -infected host cells measured by autofluorescence imaging
Gina M. Gallego-López, Emmanuel Contreras Guzman, Danielle E. Desa, Laura J. Knoll, Melissa C. Skala, Anita A. Koshy
mBio.2024;[Epub] CrossRef
BjussuLAAO-II, an l-amino acid oxidase from Bothrops jararacussu snake venom, impairs Toxoplasma gondii infection in human trophoblast cells and villous explants from the third trimester of pregnancy
Thales Alves de Melo Fernandes, Samuel Cota Teixeira, Tássia Rafaela Costa, Alessandra Monteiro Rosini, Guilherme de Souza, Lorena Polloni, Bellisa de Freitas Barbosa, Marcelo José Barbosa Silva, Eloisa Amália Vieira Ferro, Veridiana de Melo Rodrigues Ávi
Microbes and Infection.2023; 25(6): 105123. CrossRef
DNA double-strand breaks in the Toxoplasma gondii-infected cells by the action of reactive oxygen species
Haohan Zhuang, Chaoqun Yao, Xianfeng Zhao, Xueqiu Chen, Yimin Yang, Siyang Huang, Lingtao Pan, Aifang Du, Yi Yang
Parasites & Vectors.2020;[Epub] CrossRef

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Modulated Gene Expression of Toxoplasma gondii Infected Retinal Pigment Epithelial Cell Line (ARPE-19) via PI3K/Akt or mTOR Signal Pathway: Wei Zhou, Juan-Hua Quan, Fei-Fei Gao, Hassan Ahmed Hassan Ahmed Ismail, Young-Ha Lee, Guang-Ho Cha; Korean J Parasitol 2018;56(2):135-145.
Published online April 30, 2018; DOI: https://doi.org/10.3347/kjp.2018.56.2.135

Abstract
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Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- richrepeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, CK2β, VEGF, GCL, GST, and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.

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PTEN regulation in virus-associated cancers
Shaian Tavakolian, Zahra Shokati Eshkiki, Abolfazl Akbari, Ebrahim Faghihloo, Seidamir Pasha Tabaeian
Pathology - Research and Practice.2025; 266: 155749. CrossRef
MjTX-II, a Lys49-PLA2 from Bothrops moojeni snake venom, restricts Toxoplasma gondii infection via ROS and VEGF regulation
Samuel Cota Teixeira, Thales Alves de Melo Fernandes, Guilherme de Souza, Alessandra Monteiro Rosini, Aryani Felixa Fajardo Martínez, Angelica Oliveira Gomes, Rosiane Nascimento Alves, Daiana Silva Lopes, Maria Vitoria da Silva, Emidio Beraldo-Neto, Patrí
Chemico-Biological Interactions.2025; 409: 111417. CrossRef
Echinococcus multilocularis protoscoleces enhance glycolysis to promote M2 Macrophages through PI3K/Akt/mTOR Signaling Pathway
Tao Zhang, Yaogang Zhang, Zihan Yang, Yuan Jiang, Li Sun, Dengliang Huang, Meiyuan Tian, Yinhong Shen, Jun Deng, Jing Hou, Yanyan Ma
Pathogens and Global Health.2023; 117(4): 409. CrossRef
The interplay between toxoplasmosis and host miRNAs: Mechanisms and consequences
Ahmed S. Doghish, Mohamed A. Ali, Mahmoud A. Elrebehy, Hend H. Mohamed, Reda Mansour, Aml Ghanem, Ahmed Hassan, Mohammed S. Elballal, Ola Elazazy, Ahmed E. Elesawy, Sherif S. Abdel Mageed, Yara A. Nassar, Osama A. Mohammed, Ahmed I. Abulsoud
Pathology - Research and Practice.2023; 250: 154790. CrossRef
Mammalian Target of Rapamycin Inhibitor Rapamycin Alleviates 7-Ketocholesterol Induced Inflammatory Responses and Vascular Endothelial Growth Factor Elevation by Regulating MAPK Pathway in Human Retinal Pigment Epithelium Cells
Lin Yang, Peng Yu, Mei Chen, Bo Lei
Journal of Ocular Pharmacology and Therapeutics.2022; 38(2): 189. CrossRef
The host mTOR pathway and parasitic diseases pathogenesis
Sajad Rashidi, Reza Mansouri, Mohammad Ali-Hassanzadeh, Zahra Mojtahedi, Reza Shafiei, Amir Savardashtaki, Nasrin Hamidizadeh, Mohammadreza Karimazar, Paul Nguewa, Raúl Manzano-Román
Parasitology Research.2021; 120(4): 1151. CrossRef
Upregulation of PEDF Predicts a Poor Prognosis and Promotes Esophageal Squamous Cell Carcinoma Progression by Modulating the MAPK/ERK Signaling Pathway
Zui Chen, Di Che, Xiaoqiong Gu, Jiamin Lin, Jing Deng, Ping Jiang, Kaixiong Xu, Banglao Xu, Ting Zhang
Frontiers in Oncology.2021;[Epub] CrossRef
Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
Christian Rodriguez Rodrigues, María Celeste Nicolao, Maia Chop, Natalia Plá, Mora Massaro, Julia Loos, Andrea C. Cumino
Scientific Reports.2021;[Epub] CrossRef
Ripasudil alleviated the inflammation of RPE cells by targeting the miR-136-5p/ROCK/NLRP3 pathway
Zhao Gao, Qiang Li, Yunda Zhang, Xiaohong Gao, Haiyan Li, Zhigang Yuan
BMC Ophthalmology.2020;[Epub] CrossRef
H3 relaxin protects against calcium oxalate crystal‐induced renal inflammatory pyroptosis
Jiannan Liu, Kelaier Yang, Yinshan Jin, Yadong Liu, Yaodong Chen, Xiaohui Zhang, Shiliang Yu, Erlin Song, Song Chen, Jingbo Zhang, Guanhua Jing, Ruihua An
Cell Proliferation.2020;[Epub] CrossRef
Dipenyleneiodonium Induces Growth Inhibition of Toxoplasma gondii through ROS Induction in ARPE-19 Cells
Pu Reum Sun, Fei Fei Gao, Hei Gwon Choi, Wei Zhou, Jae-Min Yuk, Jaeyul Kwon, Young-Ha Lee, Guang-Ho Cha
The Korean Journal of Parasitology.2019; 57(2): 83. CrossRef
Simultaneous Ribosome Profiling of Human Host Cells Infected with Toxoplasma gondii
Michael J. Holmes, Premal Shah, Ronald C. Wek, William J. Sullivan, Ira J. Blader
mSphere.2019;[Epub] CrossRef

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IL-12 and IL-23 Production in Toxoplasma gondii- or LPS Treated Jurkat T Cells via PI3K and MAPK Signaling Pathways: Hassan Ahmed Hassan Ahmed Ismail, Byung-Hun Kang, Jae-Su Kim, Jae-Hyung Lee, In-Wook Choi, Guang-Ho Cha, Jae-Min Yuk, Young-Ha Lee; Korean J Parasitol 2017;55(6):613-622.
Published online December 31, 2017; DOI: https://doi.org/10.3347/kjp.2017.55.6.613

Abstract
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IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.

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Protective Effect of Low 2-O, 3-O Desulfated Heparin (ODSH) Against LPS-Induced Acute Lung Injury in Mice
Joyce Gonzales, Rahul S. Patil, Thomas P. Kennedy, Nagavedi S. Umapathy, Rudolf Lucas, Alexander D. Verin
Biomolecules.2025; 15(9): 1232. CrossRef
BC and 1,4NQ-BC up-regulate the cytokines and enhance IL-33 expression in LPS pretreatment of human bronchial epithelial cells☆
Jianhong Ge, Hongqian Chu, Qianqian Xiao, Weidong Hao, Jing Shang, Tong Zhu, Zhaogang Sun, Xuetao Wei
Environmental Pollution.2021; 273: 116452. CrossRef
Toxoplasma gondiiModulates the Host Cell Responses: An Overview of Apoptosis Pathways
Nour Mammari, Mohamad Adnan Halabi, Souha Yaacoub, Hilda Chlala, Marie-Laure Dardé, Bertrand Courtioux
BioMed Research International.2019; 2019: 1. CrossRef

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Brief Communication

Fasciola hepatica: Infection Status of Freshwater Snails Collected from Gangwon-do (Province), Korea: Jae-Hyung Lee, Juan-Hua Quan, In-Wook Choi, Gab-Man Park, Guang-Ho Cha, Hyun-Ju Kim, Jae-Min Yuk, Young-Ha Lee; Korean J Parasitol 2017;55(1):95-98.
Published online February 28, 2017; DOI: https://doi.org/10.3347/kjp.2017.55.1.95

Abstract
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Fasciola hepatica is a trematode that causes zoonosis, mainly in cattle and sheep, and occasionally in humans. Few recent studies have determined the infection status of this fluke in Korea. In August 2015, we collected 402 samples of freshwater snails at Hoenggye-ri (upper stream) and Suha-ri (lower stream) of Song-cheon (stream) in Daegwalnyeong-myeon, Pyeongchang-gun in Gangwon-do (Province) near many large cattle or sheep farms. F. hepatica infection was determined using PCR on the nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 402 samples, F. hepatica 1TS-2 marker was detected in 6 freshwater snails; thus, the overall prevalence in freshwater snails was 1.5%. The prevalence varied between collection areas, ranging from 0.0% at Hoenggye-ri to 2.9% at Suha-ri. However, F. gigantica ITS-2 was not detected in the 6 F. hepatica-positive samples by PCR. The nucleotide sequences of the 6 F. hepatica ITS-2 PCR-positive samples were 99.4% identical to the F. hepatica ITS-2 sequences in GenBank, whereas they were 98.4% similar to F. gigantica ITS-2 sequences. These results indicated that the prevalence of F. hepatica in snail intermediate hosts was 1.5% in Gangwon-do, Korea; however the prevalence varied between collection areas. These results may help us to understand F. hepatica infection status in natural environments.

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Original Articles

Production of IL-1β and Inflammasome with Up-Regulated Expressions of NOD-Like Receptor Related Genes in Toxoplasma gondii-Infected THP-1 Macrophages: Jia-Qi Chu, Ge Shi, Yi-Ming Fan, In-Wook Choi, Guang-Ho Cha, Yu Zhou, Young-Ha Lee, Juan-Hua Quan; Korean J Parasitol 2016;54(6):711-717.
Published online December 31, 2016; DOI: https://doi.org/10.3347/kjp.2016.54.6.711

Abstract
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Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of pro-IL-1β. To elucidate the role of inflammasome components in T. gondii-infected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine IL-1β secretion. The results revealed a significant upregulation of IL-1β after T. gondii infection. T. gondii infection also upregulated the expression of inflammasome sensors, including NLRP1, NLRP3, NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and NAIP, in a time-dependent manner. The infection also upregulated inflammasome adaptor protein ASC and caspase-1 mRNA levels. From this study, we newly found that T. gondii infection regulates NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and neuronal apoptosis inhibitor protein (NAIP) gene expressions in THP-1 macrophages and that the role of the inflammasome-related genes may be critical for mediating the innate immune responses to T. gondii infection.

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Involvement of PI3K/AKT and MAPK Pathways for TNF-α Production in SiHa Cervical Mucosal Epithelial Cells Infected with Trichomonas vaginalis: Jung-Bo Yang, Juan-Hua Quan, Ye-Eun Kim, Yun-Ee Rhee, Byung-Hyun Kang, In-Wook Choi, Guang-Ho Cha, Jae-Min Yuk, Young-Ha Lee; Korean J Parasitol 2015;53(4):371-377.
Published online August 25, 2015; DOI: https://doi.org/10.3347/kjp.2015.53.4.371

Abstract
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Trichomonas vaginalis induces proinflammation in cervicovaginal mucosal epithelium. To investigate the signaling pathways in TNF-α production in cervical mucosal epithelium after T. vaginalis infection, the phosphorylation of PI3K/AKT and MAPK pathways were evaluated in T. vaginalis-infected SiHa cells in the presence and absence of specific inhibitors. T. vaginalis increased TNF-α production in SiHa cells, in a parasite burden-dependent and incubation time-dependent manner. In T. vaginalis-infected SiHa cells, AKT, ERK1/2, p38 MAPK, and JNK were phosphorylated from 1 hr after infection; however, the phosphorylation patterns were different from each other. After pretreatment with inhibitors of the PI3K/AKT and MAPK pathways, TNF-α production was significantly decreased compared to the control; however, TNF-α reduction patterns were different depending on the type of PI3K/MAPK inhibitors. TNF-α production was reduced in a dose-dependent manner by treatment with wortmannin and PD98059, whereas it was increased by SP600125. These data suggested that PI3K/AKT and MAPK signaling pathways are important in regulation of TNF-α production in cervical mucosal epithelial SiHa cells. However, activation patterns of each pathway were different from the types of PI3K/MAPK pathways.

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Interactions between bacterial vaginosis-associated microbiota and Trichomonas vaginalis modulate parasite-induced pathogenicity and host immune responses
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PLOS ONE.2016; 11(9): e0161867. CrossRef

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Genetic Diversity of Schistosoma haematobium Eggs Isolated from Human Urine in Sudan: Juan-Hua Quan, In-Wook Choi, Hassan Ahmed Hassan Ahmed Ismail, Abdoelohab Saed Mohamed, Hoo-Gn Jeong, Jin-Su Lee, Sung-Tae Hong, Tai-Soon Yong, Guang-Ho Cha, Young-Ha Lee; Korean J Parasitol 2015;53(3):271-277.
Published online June 30, 2015; DOI: https://doi.org/10.3347/kjp.2015.53.3.271

Abstract
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The genetic diversity of Schistosoma haematobium remains largely unstudied in comparison to that of Schistosoma mansoni. To characterize the extent of genetic diversity in S. haematobium among its definitive host (humans), we collected S. haematobium eggs from the urine of 73 infected schoolchildren at 5 primary schools in White Nile State, Sudan, and then performed a randomly amplified polymorphic DNA marker ITS2 by PCR-RFLP analysis. Among 73 S. haematobium egg-positive cases, 13 were selected based on the presence of the S. haematobium satellite markers A4 and B2 in their genomic DNA, and used for RFLP analysis. The 13 samples were subjected to an RFLP analysis of the S. haematobium ITS2 region; however, there was no variation in size among the fragments. Compared to the ITS2 sequences obtained for S. haematobium from Kenya, the nucleotide sequences of the ITS2 regions of S. haematobium from 4 areas in Sudan were consistent with those from Kenya (> 99%). In this study, we demonstrate for the first time that most of the S. haematobium population in Sudan consists of a pan-African S. haematobium genotype; however, we also report the discovery of Kenyan strain inflow into White Nile, Sudan.

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Acta Tropica.2020; 204: 105363. CrossRef

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Fasciola hepatica in Snails Collected from Water-Dropwort Fields using PCR: Hwang-Yong Kim, In-Wook Choi, Yeon-Rok Kim, Juan-Hua Quan, Hassan Ahmed Hassan Ahmed Ismail, Guang-Ho Cha, Sung-Jong Hong, Young-Ha Lee; Korean J Parasitol 2014;52(6):645-652.
Published online December 23, 2014; DOI: https://doi.org/10.3347/kjp.2014.52.6.645

Abstract
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Fasciola hepatica is a trematode that causes zoonosis mainly in cattle and sheep and occasionally in humans. Fascioliasis has been reported in Korea; however, determining F. hepatica infection in snails has not been done recently. Thus, using PCR, we evaluated the prevalence of F. hepatica infection in snails at 4 large water-dropwort fields. Among 349 examined snails, F. hepatica-specific internal transcribed space 1 (ITS-1) and/or ITS-2 markers were detected in 12 snails and confirmed using sequence analysis. Morphologically, 213 of 349 collected snails were dextral shelled, which is the same aperture as the lymnaeid snail, the vectorial host for F. hepatica. Among the 12 F. hepatica-infected snails, 6 were known first intermediate hosts in Korea (Lymnaea viridis and L. ollula) and the remaining 6 (Lymnaea sp.) were potentially a new first intermediate host in Korea. It has been shown that the overall prevalence of the snails contaminated with F. hepatica in water-dropwort fields was 3.4%; however, the prevalence varied among the fields. This is the first study to estimate the prevalence of F. hepatica infection using the vectorial capacity of the snails in Korea.

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Dang Thi LOAN, Lam Thanh NGUYEN, Tran Ngoc BICH, Nguyen Thuy Y VI, Yasunobu MATSUMOTO
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Philile Ignecious Ngcamphalala, Ignore Nyagura, Mokgadi Pulane Malatji, Samson Mukaratirwa
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The Korean Journal of Parasitology.2015; 53(6): 725. CrossRef

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Trichomonas vaginalis Metalloproteinase Induces mTOR Cleavage of SiHa Cells: Juan-Hua Quan, In-Wook Choi, Jung-Bo Yang, Wei Zhou, Guang-Ho Cha, Yu Zhou, Jae-Sook Ryu, Young-Ha Lee; Korean J Parasitol 2014;52(6):595-603.
Published online December 23, 2014; DOI: https://doi.org/10.3347/kjp.2014.52.6.595

Abstract
PDF

Trichomonas vaginalis secretes a number of proteases which are suspected to be the cause of pathogenesis; however, little is understood how they manipulate host cells. The mammalian target of rapamycin (mTOR) regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. We detected various types of metalloproteinases including GP63 protein from T. vaginalis trophozoites, and T. vaginalis GP63 metalloproteinase was confirmed by sequencing and western blot. When SiHa cells were stimulated with live T. vaginalis, T. vaginalis excretory-secretory products (ESP) or T. vaginalis lysate, live T. vaginalis and T. vaginalis ESP induced the mTOR cleavage in both time- and parasite load-dependent manner, but T. vaginalis lysate did not. Pretreatment of T. vaginalis with a metalloproteinase inhibitor, 1,10-phenanthroline, completely disappeared the mTOR cleavage in SiHa cells. Collectively, T. vaginalis metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite.

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Kinetics of IL-23 and IL-12 Secretion in Response to Toxoplasma gondii Antigens from THP-1 Monocytic Cells: Juan-Hua Quan, Wei Zhou, Guang-Ho Cha, In-Wook Choi, Dae-Whan Shin, Young-Ha Lee; Korean J Parasitol 2013;51(1):85-92.
Published online February 18, 2013; DOI: https://doi.org/10.3347/kjp.2013.51.1.85

Abstract
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IL-23 and IL-12 are structurally similar and critical for the generation of efficient cellular immune responses. Toxoplasma gondii induces a strong cell-mediated immune response. However, little is known about IL-23 secretion profiles in T. gondii-infected immune cells in connection with IL-12. We compared the patterns of IL-23 and IL-12 production by THP-1 human monocytic cells in response to stimulation with live or heat-killed T. gondii tachyzoites, or with equivalent quantities of either T. gondii excretory/secretory proteins (ESP) or soluble tachyzoite antigen (STAg). IL-23 and IL-12 were significantly increased from 6 hr after stimulation with T. gondii antigens, and their secretions were increased with parasite dose-dependent manner. IL-23 concentrations were significantly higher than those of IL-12 at the same multiplicity of infection. IL-23 secretion induced by live parasites was significantly higher than that by heat-killed parasites, ESP, or STAg, whereas IL-12 secretion by live parasite was similar to those of ESP or STAg. However, the lowest levels of both cytokines were at stimulation with heat-killed parasites. These data indicate that IL-23 secretion patterns by stimulation with various kinds of T. gondii antigens at THP-1 monocytic cells are similar to those of IL-12, even though the levels of IL-23 induction were significantly higher than those of IL-12. The detailed kinetics induced by each T. gondii antigen were different from each other.

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T. gondii excretory proteins promote the osteogenic differentiation of human bone mesenchymal stem cells via the BMP/Smad signaling pathway
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Gene Expression Profiles in Genetically Different Mice Infected with Toxoplasma gondii: ALDH1A2, BEX2, EGR2, CCL3 and PLAU: Hassan Ahmed Hassan Ahmed Ismail, Juan-Hua Quan, Zhou Wei, In-Wook Choi, Guang-Ho Cha, Dae-Whan Shin, Young-Ha Lee, Chang-June Song; Korean J Parasitol 2012;50(1):7-13.
Published online March 6, 2012; DOI: https://doi.org/10.3347/kjp.2012.50.1.7

Abstract
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Toxoplasma gondii can modulate host cell gene expression; however, determining gene expression levels in intermediate hosts after T. gondii infection is not known much. We selected 5 genes (ALDH1A2, BEX2, CCL3, EGR2 and PLAU) and compared the mRNA expression levels in the spleen, liver, lung and small intestine of genetically different mice infected with T. gondii. ALDH1A2 mRNA expressions of both mouse strains were markedly increased at day 1-4 postinfection (PI) and then decreased, and its expressions in the spleen and lung were significantly higher in C57BL/6 mice than those of BALB/c mice. BEX2 and CCR3 mRNA expressions of both mouse strains were significantly increased from day 7 PI and peaked at day 15-30 PI (P<0.05), especially high in the spleen liver or small intestine of C57BL/6 mice. EGR2 and PLAU mRNA expressions of both mouse strains were significantly increased after infection, especially high in the spleen and liver. However, their expression patterns were varied depending on the tissue and mouse strain. Taken together, T. gondii-susceptible C57BL/6 mice expressed higher levels of these 5 genes than did T. gondii-resistant BALB/c mice, particularly in the spleen and liver. And ALDH1A2 and PLAU expressions were increased acutely, whereas BEX2, CCL3 and EGR2 expressions were increased lately. Thus, these demonstrate that host genetic factors exert a strong impact on the expression of these 5 genes and their expression patterns were varied depending on the gene or tissue.

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Proteomic Analysis of Toxoplasma gondii KI-1 Tachyzoites: Si-Hwan Choi, Tae Yun Kim, Sung Goo Park, Guang-Ho Cha, Dae-Whan Shin, Jong-Yil Chai, Young-Ha Lee; Korean J Parasitol 2010;48(3):195-201.
Published online September 16, 2010; DOI: https://doi.org/10.3347/kjp.2010.48.3.195

Abstract
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We studied on the proteomic characteristics of Toxoplasma gondii KI-1 tachyzoites which were originally isolated from a Korean patient, and compared with those of the well-known virulent RH strain using 2-dimensional electrophoresis (2-DE), mass spectrometry, and quantitative real-time PCR. Two-dimensional separation of the total proteins isolated from KI-1 tachyzoites revealed up to 150 spots, of which 121 were consistent with those of RH tachyzoites. Of the remaining 29 spots, 14 showed greater than 5-fold difference in density between the KI-1 and RH tachyzoites at a pH of 5.0-8.0. Among the 14 spots, 5 from the KI-1 isolate and 7 from the RH strain were identified using MALDI-TOF mass spectrometry and database searches. The spots from the KI-1 tachyzoites were dense granule proteins (GRA 2, 3, 6, and 7), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGRPTase), and uracil phosphoribosyltransferase (UPRTase). The spots from the RH strain were surface antigen 1 (SAG 1), L-lactate dehydrogenase (LDH), actin, chorismate synthase, peroximal catalase, hexokinase, bifunctional dihydrofolate reductase-thymidylate synthase (DHTR-TS), and nucleoside-triphosphatases (NTPases). Quantitative real-time PCR supported our mass spectrometric results by showing the elevated expression of the genes encoding GRA 2, 3, and 6 and UPRTase in the KI-1 tachyzoites and those encoding GRA 7, SAG 1, NTPase, and chorismate synthase in the RH tachyzoites. These observations demonstrate that the protein compositions of KI-1 and RH tachyzoites are similar but differential protein expression is involved in virulence.

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Brief Communication

Antigenemia and Specific IgM and IgG Antibody Responses in Rabbits Infected with Toxoplasma gondii: Juan Hua Quan, Hassan Ahmed Hassan, Guang-Ho Cha, Dae-Whan Shin, Young-Ha Lee; Korean J Parasitol 2009;47(4):409-412.
Published online December 1, 2009; DOI: https://doi.org/10.3347/kjp.2009.47.4.409

Abstract
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In this experiment, the correlation between antigenemia and specific antibody responses in Toxoplasma gondii-infected rabbits was assessed. We injected 1,000 T. gondii tachyzoites (RH) subcutaneously into 5 rabbits. Parasitemia, circulating antigens, and IgM and IgG antibody titers in blood were tested by ELISA and immunoblot. For detection of parasitemia, mice were injected with blood from rabbits infected with T. gondii and mice died between days 2 and 10 post-infection (PI). Circulating antigens were detected early on day 2 PI, and the titers increased from day 4 PI and peaked on day 12 PI. Anti-Toxoplasma IgM antibody titers increased on day 6 PI and peaked on days 14-16 PI. IgG was detected from day 10 PI, and the titers increased continuously during the experiment. The antigenic protein patterns differed during the infection period, and the number of bands increased with ongoing infection by the immunoblot analysis. These result indicated that Toxoplasma circulating antigens during acute toxoplasmosis are closely related to the presence of parasites in blood. Also, the circulating antigen levels were closely correlated with IgM titers, but not with IgG titers. Therefore, co-detection of circulating antigens with IgM antibodies may improve the reliability of the diagnosis of acute toxoplasmosis.

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Original Article

Seroprevalence of Toxoplasma gondii Infection and Characteristics of Seropositive Patients in General Hospitals in Daejeon, Korea: Dae-Whan Shin, Dong-Yeub Cha, Quan Juan Hua, Guang-Ho Cha, Young-Ha Lee; Korean J Parasitol 2009;47(2):125-130.
Published online May 27, 2009; DOI: https://doi.org/10.3347/kjp.2009.47.2.125

Abstract
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To figure out the epidemiological status and relevance with other diseases in toxoplasmosis, we checked serum IgG antibody titers of 1,265 patients and medical records of seropositive patients. Seropositive rates were 6.6% by latex agglutination test (LAT) and 6.7% by ELISA. No significant differences were detected between sexes and age groups. The peak seroprevalence was detected in the 40-49-year-old age group. According to clinical department, Toxoplasma-positive rates were high in patients in psychiatry, ophthalmology, health management, emergency medicine, and thoracic surgery. Major coincidental diseases in seropositive cases were malignant neoplasms, diabetes mellitus, arthritis, chronic hepatitis B, chronic renal diseases, schizophrenia, and acute lymphadenitis, in the order of frequency. In particular, some patients with chronic hepatitis B and malignant neoplasms had high antibody titers. These results revealed that the seroprevalence of toxoplasmosis in a general hospital-based study was similar to that in a community-based study, and T. gondii seropositivity may be associated with neoplasms, diabetes, and other chronic infections.

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