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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.

Citations

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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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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.

Citations

Citations to this article as recorded by  Crossref logo
  • 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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  • 198 Download
  • 5 Web of Science
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Brief Communications

Immunogenicity of Exosomes from Dendritic Cells Stimulated with Toxoplasma gondii Lysates in Ocularly Immunized Mice
Bong-Kwang Jung, Eun-Do Kim, Hyemi Song, Jong-Yil Chai, Kyoung Yul Seo
Korean J Parasitol 2020;58(2):185-189.
Published online April 30, 2020
DOI: https://doi.org/10.3347/kjp.2020.58.2.185
Immunogenicity of dendritic cell-derived exosomes stimulated with Toxoplasma gondii lysates (TLA exo), mixed with cholera toxin as an adjuvant, was investigated in mice immunized via 2 mucosal routes (ocular vs intranasal). BALB/c mice were injected 3 times with TLA exo vaccine at 2 week interval, and the levels of IgG in serum and IgA in tear, saliva, feces, and vaginal wash were measured. To observe the expression of T. gondii-specific B1 gene, mice infected with ME49 T. gondii cysts were immunized with TLA exo or PBS exo (not stimulated with TLA), and their brain tissues were examined. The mice vaccinated via intranasal route elicited significantly higher humoral and mucosal immune responses compared with mice treated with PBS alone. Also, mice immunized via ocular route (by eyedrop) induced significantly higher T. gondii-specific IgG in serum and IgA in tear and feces in comparison with PBS controls. B1 gene expression was significantly lower in TLA exo vaccinated mice than in PBS or PBS exo vaccinated mice. These results demonstrated that ocular immunization of mice with TLA exo vaccine has the potential to stimulate systemic or local antibody responses. This study also highlighted an advantage of an eyedrop vaccine as an alternative for T. gondii intranasal vaccines.

Citations

Citations to this article as recorded by  Crossref logo
  • Bridging biology and therapy: translational advances of extracellular vesicles in veterinary clinical practice
    Walaa A. Gad, Sally Ibrahim, Hiam Nagdy, Bassma S. M. Elsawy, Dina Aboelsoued, Hoda S. M. Abdel-Ghany, Ahmed A. A. Abdel-Wareth, Khaled A. Abd El-Razik, Karima Gh. M. Mahmoud, Walid T. M. Soliman, Mohamed O. Taqi
    Veterinary Research Communications.2026;[Epub]     CrossRef
  • Emerging role of extracellular vesicles in veterinary practice: novel opportunities and potential challenges
    Yindi Xiong, Peng Lou, Chuang Xu, Bo Han, Jingping Liu, Jian Gao
    Frontiers in Veterinary Science.2024;[Epub]     CrossRef
  • The End Justifies the Means: Chagas Disease from a Perspective of the Host–Trypanosoma cruzi Interaction
    Izadora Volpato Rossi, Denise Andréa Silva de Souza, Marcel Ivan Ramirez
    Life.2024; 14(4): 488.     CrossRef
  • Exosomes: from biology to immunotherapy in infectious diseases
    Velia Verónica Rangel-Ramírez, Hilda Minerva González-Sánchez, César Lucio-García
    Infectious Diseases.2023; 55(2): 79.     CrossRef
  • The potential application of encapsulated exosomes: A new approach to increase exosomes therapeutic efficacy
    Ali Hazrati, Zahra Mirsanei, Neda Heidari, Kosar Malekpour, Nasim Rahmani-Kukia, Ardeshir Abbasi, Sara Soudi
    Biomedicine & Pharmacotherapy.2023; 162: 114615.     CrossRef
  • Host-pathogen interactions mediated by extracellular vesicles in Toxoplasma gondii infection during pregnancy
    Fernando Gómez-Chávez, José M. Murrieta-Coxca, Heriberto Caballero-Ortega, Diana M. Morales-Prieto, Udo R. Markert
    Journal of Reproductive Immunology.2023; 158: 103957.     CrossRef
  • Immune system roles in pathogenesis, prognosis, control, and treatment of Toxoplasma gondii infection
    Mohammad Mahdi Jafari, Zahra Azimzadeh Tabrizi, Mohammad Saaid Dayer, Nazanin Atieh Kazemi-Sefat, Mahshid Mohtashamifard, Rahimeh Mohseni, Atefeh Bagheri, Saeed Bahadory, Amir Karimipour-Saryazdi, Fatemeh Ghaffarifar
    International Immunopharmacology.2023; 124: 110872.     CrossRef
  • Liquid Biopsy for Promising Non-invasive Diagnostic Biomarkers in Parasitic Infections
    Eylem Akdur Ozturk, Ayse Caner
    Acta Parasitologica.2022; 67(1): 1.     CrossRef
  • Eyedrop vaccination: an immunization route with promises for effective responses to pandemics
    Jihei Sara Lee, Sangchul Yoon, Soo Jung Han, Eun-Do Kim, Jiyeon Kim, Hae-Sol Shin, Kyoung Yul Seo
    Expert Review of Vaccines.2022; 21(1): 91.     CrossRef
  • Extracellular vesicles from Trypanosoma cruzi-dendritic cell interaction show modulatory properties and confer resistance to lethal infection as a cell-free based therapy strategy
    Brenda Celeste Gutierrez, Maria Eugenia Ancarola, Izadora Volpato-Rossi, Antonio Marcilla, Marcel Ivan Ramirez, Mara Cecilia Rosenzvit, Marcela Cucher, Carolina Verónica Poncini
    Frontiers in Cellular and Infection Microbiology.2022;[Epub]     CrossRef
  • Chemically Engineered Immune Cell‐Derived Microrobots and Biomimetic Nanoparticles: Emerging Biodiagnostic and Therapeutic Tools
    Leila Pourtalebi Jahromi, Mohammad‐Ali Shahbazi, Aziz Maleki, Amir Azadi, Hélder A. Santos
    Advanced Science.2021;[Epub]     CrossRef
  • Exosome-Based Vaccines: History, Current State, and Clinical Trials
    Patrick Santos, Fausto Almeida
    Frontiers in Immunology.2021;[Epub]     CrossRef
  • 6,664 View
  • 117 Download
  • 12 Web of Science
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Sparganosis is a tissue invading helminthiasis infecting intermediate hosts, including humans. Strong immune responses are expected to occur in early phases of infection. Thus, we investigated cytokine expressions in splenic dendritic cells and in sera after experimental infection of mice. In splenic dendritic cells, TNF-α and IL-1β expression peaked at week 1 and week 3 post-infection (PI), respectively, and also early phase (week 2 PI) depressed cytokine expression was noticed. Serum IL-1β concentration increased significantly at week 2 PI and peaked at week 6 PI, and that of TNF-α peaked at week 6 PI. These results showed that pro-inflammatory cytokines, TNF-α and IL-1β, are chronologically regulated in mouse sparganosis.

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Original Article
Pro-inflammatory Cytokine Expression of Spleen Dendritic Cells in Mouse Toxoplasmosis
Ho-Woo Nam, Hye-Jin Ahn, Hyun-Jong Yang
Korean J Parasitol 2011;49(2):109-114.
Published online June 14, 2011
DOI: https://doi.org/10.3347/kjp.2011.49.2.109

Dendritic cells have been known as a member of strong innate immune cells against infectious organelles. In this study, we evaluated the cytokine expression of splenic dendritic cells in chronic mouse toxoplasmosis by tissue cyst-forming Me49 strain and demonstrated the distribution of lymphoid dendritic cells by fluorescence-activated cell sorter (FACS). Pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, and IL-10 increased rapidly at week 1 post-infection (PI) and peaked at week 3 PI. Serum IL-10 level followed the similar patterns. FACS analysis showed that the number of CD8α+/CD11c+ splenic dendritic cells increased at week 1 and peaked at week 3 PI. In conclusion, mouse splenic dendritic cells showed early and rapid cytokine changes and may have important protective roles in early phases of murine toxoplasmosis.

Citations

Citations to this article as recorded by  Crossref logo
  • 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 and Diseases.2023; 61(2): 138.     CrossRef
  • Impact of intrarectal chromofungin treatment on dendritic cells-related markers in different immune compartments in colonic inflammatory conditions
    Kunal Kapoor, Nour Eissa, Diane Tshikudi, Charles N Bernstein, Jean-Eric Ghia
    World Journal of Gastroenterology.2021; 27(47): 8138.     CrossRef
  • Multi-Omics Studies Demonstrate Toxoplasma gondii-Induced Metabolic Reprogramming of Murine Dendritic Cells
    Kerrie E. Hargrave, Stuart Woods, Owain Millington, Susan Chalmers, Gareth D. Westrop, Craig W. Roberts
    Frontiers in Cellular and Infection Microbiology.2019;[Epub]     CrossRef
  • Tissue Fluid Enzyme-Linked Immunosorbant Assay for Piglets Experimentally Infected with Toxoplasma gondii and Survey on Local and Imported Pork in Korean Retail Meat Markets
    Won Gi Yoo, Sun-Min Kim, Eun Jeong Won, Ji-Yun Lee, Fuhong Dai, Ho Choon Woo, Ho-Woo Nam, Tae Im Kim, Jeong-Hee Han, Dongmi Kwak, Yun Sang Cho, Seung-Won Kang, Tong-Soo Kim, Xing-Quan Zhu, Chunren Wang, Heejeong Youn, Sung-Jong Hong
    The Korean Journal of Parasitology.2018; 56(5): 437.     CrossRef
  • Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes
    Eva Znalesniak, Ting Fu, Franz Salm, Ulrike Händel, Werner Hoffmann
    International Journal of Molecular Sciences.2017; 18(6): 1245.     CrossRef
  • Toxoplasmosis treatment with diphenyl diselenide in infected mice modulates the activity of purinergic enzymes and reduces inflammation in spleen
    Pedro H. Doleski, Maura V. Ten Caten, Daniela F. Passos, Lívia G. Castilhos, Daniela B.R. Leal, Vanessa S. Machado, Nathieli B. Bottari, Fernanda F. Vogel, Ricardo E. Mendes, Aleksandro Schafer da Silva
    Experimental Parasitology.2017; 181: 7.     CrossRef
  • Dectin-1-CD37 association regulates IL-6 expression during Toxoplasma gondii infection
    Junping Yan, Bin Wu, Bo Huang, Shiguang Huang, Suhua Jiang, Fangli Lu
    Parasitology Research.2014; 113(8): 2851.     CrossRef
  • 8,684 View
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