Toxoplasma gondii is an obligate intracellular protozoan parasite, which invades a wide range of hosts including humans. The exact mechanisms involved in its invasion are not fully understood. This study focused on the roles of Ca2+ in host cell invasion and in T. gondii replication. We examined the invasion and replication of T. gondii pretreated with several calcium modulators, the conoid extrusion of tachyzoites. Calmodulin localization in T. gondii were observed using the immunogold method, and Ca2+ levels in tachyzoites by confocal microscopy. In light microscopic observation, tachyzoites co-treated with A23187 and EGTA showed that host cell invasion and intracellular replication were decreased. The invasion of tachyzoites was slightly inhibited by the Ca2+ channel blockers, bepridiland verapamil, and by the calmodulin antagonist, calmidazolium. We observed that calcium saline containing A23187 induced the extrusion of tachyzoite conoid. By immunoelectron microscopy, gold particles bound to anti-calmodulin or anti-actin mAb, were found to be localized on the anterior portion of tachyzoites. Remarkably reduced intracellular Ca2+ was observed in tachyzoites treated with BAPTA/AM by confocal microscopy. These results suggest that host cell invasion and the intracellular replication of T. gondii tachyzoites are inhibited by the calcium ionophore, A23187, and by the extracellular calcium chelator, EGTA.
Citations
Citations to this article as recorded by
Unveiling the impact of cGMP-dependent protein kinase of Neospora caninum on calcium fluxes and egress functions through quantitative phosphoproteome analysis Xianmei Wang, Kun Guo, Zhili Shan, Zhu Ying, Zifu Zhu, Shiman Yang, Na Yang, Qun Liu, Lifang Wang, Jing Liu Communications Biology.2025;[Epub] CrossRef
Microfluidic model for in vitro acute Toxoplasma gondii infection and transendothelial migration Hyunho Kim, Sung-Hee Hong, Hyo Eun Jeong, Sewoon Han, Jinchul Ahn, Jin-A. Kim, Ji-Hun Yang, Hyun Jeong Oh, Seok Chung, Sang-Eun Lee Scientific Reports.2022;[Epub] CrossRef
Toxoplasma gondiiinfection and risk of attention-deficit hyperactivity disorder: a systematic review and meta-analysis Tooran Nayeri, Shahabeddin Sarvi, Mahmood Moosazadeh, Zahra Hosseininejad, Afsaneh Amouei, Ahmad Daryani Pathogens and Global Health.2020; 114(3): 126. CrossRef
Effects of Toxoplasma gondii infection on the function and integrity of human cerebrovascular endothelial cells and the influence of verapamil treatment in vitro M.S.R. Harun, Victoria Marsh, Nashwa A. Elsaied, Kevin F. Webb, Hany M. Elsheikha Brain Research.2020; 1746: 147002. CrossRef
Resistance towards monensin is proposed to be acquired in aToxoplasma gondiimodel by reduced invasion and egress activities, in addition to increased intracellular replication AHMED THABET, JOHANNES SCHMIDT, SVEN BAUMANN, WALTHER HONSCHA, MARTIN VON BERGEN, ARWID DAUGSCHIES, BERIT BANGOURA Parasitology.2018; 145(3): 313. CrossRef
Anti-Toxoplasmosis Effect of the Herbal Extracts Plantago asiatica L. Sunhwa Hong, Okjin Kim Korean Journal of Plant Resources.2016; 29(1): 26. CrossRef
Anti-Toxoplasmosis effects of herbal extracts against Toxoplasma Gondii Sunhwa Hong, Hyun-A Lee, Yung-Ho Chung, Tae-Wan Kim, Okjin Kim Korean Journal of Veterinary Service.2014; 37(2): 101. CrossRef
Anti-Toxoplasmosis Effect of Meliae fructus Ethanol Extract Hak-Yong Lee, Okjin Kim Journal of Biomedical Research.2014; 15(4): 189. CrossRef
Anti-Toxoplasmosis Effect of the Halophyte Suaeda maritime Sunhwa Hong, Hyun-A Lee, Yun-Seong Lee, Dong-Woo Kim, Jae-Hyeok Jeong, Tae-Wan Kim, Okjin Kim Korean Journal of Plant Resources.2014; 27(5): 415. CrossRef
Anti-toxoplasmosis effect of Dictamnus dasycarpus extract against Toxoplasma Gondii Sunhwa Hong, Hyun-A Lee, Yun-seong Lee, Yung-Ho Chung, Okjin Kim Journal of Biomedical Research.2014; 15(1): 7. CrossRef
Interplay of host–pathogen microvesicles and their role in infectious disease Jameel M. Inal, Ephraim A. Ansa-Addo, Sigrun Lange Biochemical Society Transactions.2013; 41(1): 258. CrossRef
The effect of kinase, actin, myosin and dynamin inhibitors on host cell egress by Toxoplasma gondii Lucio Ayres Caldas, Sergio Henrique Seabra, Márcia Attias, Wanderley de Souza Parasitology International.2013; 62(5): 475. CrossRef
Toxoplasmosis and Polygenic Disease Susceptibility Genes: ExtensiveToxoplasma gondiiHost/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders C. J. Carter Journal of Pathogens.2013; 2013: 1. CrossRef
In vitro effects of aqueous extracts of Astragalus membranaceus and Scutellaria baicalensis GEORGI on Toxoplasma gondii Xiaoyan Yang, Bo Huang, Jianping Chen, Shiguang Huang, Huanqin Zheng, Zhao-Rong Lun, Jilong Shen, Yong Wang, Fangli Lu Parasitology Research.2012; 110(6): 2221. CrossRef
Simple and efficient model systems of screening anti-Toxoplasmadrugsin vitro Chunmei Jin, Suk-Yul Jung, Sung Yeon Kim, Hyun-Ok Song, Hyun Park Expert Opinion on Drug Discovery.2012; 7(3): 195. CrossRef
Identification of Putative Potassium Channel Homologues in Pathogenic Protozoa David L. Prole, Neil V. Marrion, Gordon Langsley PLoS ONE.2012; 7(2): e32264. CrossRef
In vitro and experimental therapeutic studies of the calcium channel blocker bepridil: Detection of viable Leishmania (L.) chagasi by real-time PCR Juliana Q. Reimão, Fábio A. Colombo, Vera L. Pereira-Chioccola, André G. Tempone Experimental Parasitology.2011; 128(2): 111. CrossRef
Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs Juliana Quero Reimão, André Gustavo Tempone Memórias do Instituto Oswaldo Cruz.2011; 106(8): 1032. CrossRef
Microscopic analysis of calcium ionophore activated egress of Toxoplasma gondii from the host cell Lucio Ayres Caldas, Wanderley de Souza, Márcia Attias Veterinary Parasitology.2010; 167(1): 8. CrossRef
Induction and regulation of conoid extrusion inToxoplasma gondii M. González Del Carmen, M. Mondragón, S. González, R. Mondragón Cellular Microbiology.2009; 11(6): 967. CrossRef
THE IMPORTANCE OF TOXOPLASMA GONDII INFECTION IN DISEASES PRESENTING WITH HEADACHES. HEADACHES AND ASEPTIC MENINGITIS MAY BE MANIFESTATIONS OF THE JARISCH-HERXHEIMER REACTION JOSEPH PRANDOTA International Journal of Neuroscience.2009; 119(12): 2144. CrossRef
Idiopatyczne nadciśnienie śródczaszkowe, guz rzekomy czaszki oraz aseptyczne zapalenie opon mogą być spowodowane reaktywacją latentnej toksoplazmozy mózgowej Józef Prandota Pediatria Polska.2009; 84(5): 453. CrossRef
Characterization of a New Gene <italic>wx2</italic> in <italic>Toxoplasma gondii</italic> Xiang Wu, Qiong Zhang, Kui Tan, Ronghua Xie, Jiubo Fan, Hengping Shu, Shiping Wang Acta Biochimica et Biophysica Sinica.2007; 39(7): 475. CrossRef
Laser scanning cytometer‐based assays for measuring host cell attachment and invasion by the human pathogen Toxoplasma gondii Jeffrey Mital, Janet Schwarz, Douglas J. Taatjes, Gary E. Ward Cytometry Part A.2006; 69A(1): 13. CrossRef
Although some reports have been published on the protective effect of antibodies to Toxoplasma gondii surface membrane proteins, few address the inhibitory activity of antibodies to dense granular proteins (GRA proteins). Therefore, we performed a series of experiments to evaluate the inhibitory effects of monoclonal antibodies (mAbs) to GRA proteins (GRA2, 28 kDa; GRA6, 32 kDa) and surface membrane protein (SAG1, 30 kDa) on the invasion of T. gondii tachyzoites. Passive immunization of mice with one of three mAbs following challenge with a lethal dose of tachyzoites significantly increased survival compared with results for mice treated with control ascites. The survival times of mice challenged with tachyzoites pretreated with anti-GRA6 or anti-SAG1 mAb were significantly increased. Mice that received tachyzoites pretreated with both mAb and complement had longer survival times than those that received tachyzoites pretreated with mAb alone. Invasion of tachyzoites into fibroblasts and macrophages was significantly inhibited in the anti-GRA2, anti-GRA6 or anti-SAG1 mAb pretreated group. Pretreatment with mAb and complement inhibited invasion of tachyzoites in both fibroblasts and macrophages. These results suggest that specific antibodies to dense-granule molecules may be useful for controlling infection with T. gondii.
Citations
Citations to this article as recorded by
Different kinetics of humoral response against individual antigens in the ovine model of Toxoplasma gondii infection and its pathological association Paula Formigo, Ignacio Gual, Germán J. Cantón, Luisa F. Mendoza Morales, Emiliano Sosa, Agustina Soto Cabrera, Valeria Scioli, Claudia Morsella, Valeria A. Sander, Dadin P. Moore, Sergio O. Angel, Lucía M. Campero, Marina Clemente Frontiers in Immunology.2025;[Epub] 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
A Novel Vaccine Candidate: Recombinant Toxoplasma gondii Perforin-Like Protein 2 Stimulates Partial Protective Immunity Against Toxoplasmosis Xiaowei Tian, Hanqi Sun, Meng Wang, Guangmin Wan, Tong Xie, Xuefang Mei, Zhenchao Zhang, Xiangrui Li, Shuai Wang Frontiers in Veterinary Science.2022;[Epub] CrossRef
Control of human toxoplasmosis Nicholas C. Smith, Cibelly Goulart, Jenni A. Hayward, Andreas Kupz, Catherine M. Miller, Giel G. van Dooren International Journal for Parasitology.2021; 51(2-3): 95. CrossRef
Engineering and Functional Evaluation of Neutralizing Antibody Fragments Against Congenital Toxoplasmosis Anne di Tommaso, Matthieu O Juste, Zineb Lakhrif, Marie-Noëlle Mévélec, Coraline Borowczyk, Pierre Hammeni, Guillaume Désoubeaux, Nathalie Van Langendonck, Françoise Debierre-Grockiego, Nicolas Aubrey, Isabelle Dimier-Poisson The Journal of Infectious Diseases.2021; 224(4): 705. CrossRef
Treatment of toxoplasmosis: Current options and future perspectives Neda Konstantinovic, Hélène Guegan, Tijana Stäjner, Sorya Belaz, Florence Robert-Gangneux Food and Waterborne Parasitology.2019; 15: e00036. CrossRef
Toxoplasma gondii-positive human sera recognise intracellular tachyzoites and bradyzoites with diverse patterns of immunoreactivity Marijo S. Roiko, Kaice LaFavers, Diane Leland, Gustavo Arrizabalaga International Journal for Parasitology.2018; 48(3-4): 225. CrossRef
Interferon-γ-dependent protection against Neospora caninum infection conferred by mucosal immunization in IL-12/IL-23 p40-deficient mice Pedro Ferreirinha, Ricardo Fróis-Martins, Luzia Teixeira, António Rocha, Manuel Vilanova, Alexandra Correia Vaccine.2018; 36(32): 4890. CrossRef
Plant-derived chimeric antibodies inhibit the invasion of human fibroblasts byToxoplasma gondii Sherene Swee Yin Lim, Kek Heng Chua, Greta Nölke, Holger Spiegel, Wai Leong Goh, Sek Chuen Chow, Boon Pin Kee, Rainer Fischer, Stefan Schillberg, Rofina Yasmin Othman PeerJ.2018; 6: e5780. CrossRef
Toxoplasma gondii Elongation Factor 1-Alpha (TgEF-1α) Is a Novel Vaccine Candidate Antigen against Toxoplasmosis Shuai Wang, Zhenchao Zhang, Yujian Wang, Javaid A. Gadahi, Lixin Xu, Ruofeng Yan, Xiaokai Song, Xiangrui Li Frontiers in Microbiology.2017;[Epub] CrossRef
Evaluation of Immunoprotection Conferred by the Subunit Vaccines of GRA2 and GRA5 against Acute Toxoplasmosis in BALB/c Mice Xiao T. Ching, Mun Y. Fong, Yee L. Lau Frontiers in Microbiology.2016;[Epub] CrossRef
Recent Advances in Toxoplasma gondii Immunotherapeutics Sherene Swee-Yin Lim, Rofina Yasmin Othman The Korean Journal of Parasitology.2014; 52(6): 581. CrossRef
Generation of a Neutralizing Human Monoclonal Antibody Fab Fragment to Surface Antigen 1 ofToxoplasma gondiiTachyzoites Yong-Feng Fu, Meng Feng, Kenji Ohnishi, Tamon Kimura, Johbu Itoh, Xun-Jia Cheng, Hiroshi Tachibana, J. H. Adams Infection and Immunity.2011; 79(1): 512. CrossRef
GRA Proteins of Toxoplasma gondii: Maintenance of Host-Parasite Interactions across the Parasitophorous Vacuolar Membrane Ho-Woo Nam The Korean Journal of Parasitology.2009; 47(Suppl): S29. CrossRef
Protective Th1 immune responses against chronic toxoplasmosis induced by a protein–protein vaccine combination but not by its DNA–protein counterpart E. Jongert, D. Verhelst, M. Abady, E. Petersen, N. Gargano Vaccine.2008; 26(41): 5289. CrossRef
Evaluation of protective effect of recombinant dense granule antigens GRA2 and GRA6 formulated in monophosphoryl lipid A (MPL) adjuvant against Toxoplasma chronic infection in mice Majid Golkar, Mohammad-Ali Shokrgozar, Sima Rafati, Karine Musset, Mehdi Assmar, Reza Sadaie, Marie-France Cesbron-Delauw, Corinne Mercier Vaccine.2007; 25(21): 4301. CrossRef
First
Prev
