Shavi Ritika and NL Selokar and MK Singh*

Embryo Biotechnology Lab, Animal Biotechnology Division, ICAR- National Dairy Research Institute, Haryana, India

*Corresponding Author: MK Singh, Embryo Biotechnology Lab, Animal Biotechnology Division, ICAR- National Dairy Research Institute, Haryana, India.

Received: June 13, 2025; Published: July 23, 2025

Abstract

Toxoplasma gondii is a globally distributed, obligate intracellular parasite that infects virtually all warm-blooded animals, in cluding humans. Although infection is typically asymptomatic in immunocompetent individuals, it can lead to severe disease in im munocompromised patients and fetuses during congenital transmission. The parasite’s ability to persist lifelong within host tissues, particularly in immune-privileged sites such as the brain and eyes, underscores its complex strategies for host manipulation and immune evasion.

This review focuses on recent advances in the understanding of T. gondii pathogenesis, with a particular emphasis on host–para site interactions, molecular mechanisms of immune evasion, and emerging therapeutic approaches. We explore the role of key ef fector proteins-especially rhoptry (ROPs) and dense granule (GRAs)-in altering host immune signaling, suppressing inflammatory responses, and promoting intracellular survival. Recent findings on mitochondrial hijacking through host mitochondrial association (HMA) and modulation of host non-coding RNAs further reveal the parasite’s sophisticated manipulation of host cell biology.

Chronic toxoplasmosis remains a major therapeutic challenge, as existing treatments such as pyrimethamine-sulfadiazine are ef fective only against the actively replicating tachyzoite stage and have significant toxicity. This review discusses novel treatment strat egies including apicoplast-targeting agents, host-directed therapies, nanoparticle drug delivery systems, and CRISPR-Cas9-based functional genomic approaches to identify essential parasite genes and new drug targets.

This review aims to provide a comprehensive and current perspective on T. gondii’s biology and pathogenesis. The review also highlights gaps in current knowledge, such as the limited understanding of bradyzoite persistence mechanisms and ineffective cyst targeted therapies. By narrowing our focus to the mechanistic and therapeutic aspects of T. gondii, we aim to inform future research and guide the development of more effective interventions against both acute and chronic toxoplasmosis.

Keywords: miRNA; Embryos; Pluripotency; Epigenetic Modifications

References

1. Kochanowsky Joshua A and Anita A Koshy. “Toxoplasma gondii”. Current Biology : CB14 (2018): R770-R771.
2. Attias Márcia., et al. “The life-cycle of Toxoplasma gondii reviewed using animations”. Parasites and Vectors1 (2020): 588.
3. Hunter Christopher A and L David Sibley. “Modulation of innate immunity by Toxoplasma gondii virulence effectors”. Nature Reviews. Microbiology11 (2012): 766-778.
4. Medina Lisvaneth., et al. “Trypanosoma cruziand Toxoplasma gondii Induce a Differential MicroRNA Profile in Human Placental Explants”. Frontiers in Immunology 11 (2020): 595250.
5. Pan Ming., et al. “The determinants regulating Toxoplasma gondiibradyzoite development”. Frontiers in Microbiology 13 (2022): 1027073.
6. Dunay Ildiko Rita., et al. “Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice”. Clinical Microbiology Reviews4 (2018): e00057-17.
7. Elsheikha Hany M., et al. “Epidemiology, Pathophysiology, Diagnosis, and Management of Cerebral Toxoplasmosis”. Clinical Microbiology Reviews1 (2022): e00115-119.
8. Elmore SA., et al. “Toxoplasma gondii: Epidemiology and Control”. Veterinary Parasitology2-4 (2010): 145-153.
9. Furtado João M., et al. “Toxoplasmosis: A Global Threat”. Current Ophthalmology Reports1 (2016): 67-74.
10. Petersen Esben., et al. “What Do We Know About Risk Factors for Infection in Humans with Toxoplasma gondii and How Can We Prevent Infections?" Zoonoses and Public Health1 (2010): 8-17.
11. Flegr Jaroslav., et al. “Toxoplasmosis: A Global Threat and Its Possible Links to Mental Disorders and Behavioral Changes”. Folia Parasitologica 6 (2014).
12. Saadatnia Gilda and Davood Golkar. "A Review on Human Toxoplasmosis”. Scandinavian Journal of Infectious Diseases11 (2012): 805-814.
13. Attias Márcia., et al. “The life-cycle of Toxoplasma gondii reviewed using animations”. Parasites and Vectors1 (2020): 588.
14. Tenter Astrid M., et al. “Toxoplasma gondii: from animals to humans”. International journal for Parasitology12-13 (2000): 1217-1258.
15. Dubey JP. "Advances in the life cycle of Toxoplasma gondii”. International Journal for Parasitology7 (1998): 1019-1024.
16. Gissot Mathieu. "Toxoplasma gondii: Asexual Cycle in the Intermediate Host”. Lifecycles of Pathogenic Protists in Humans. Cham: Springer International Publishing (2022): 391-417.
17. Jeffers Victoria., et al. “A latent ability to persist: differentiation in Toxoplasma gondii”. Cellular and Molecular Life Sciences : CMLS13 (2018): 2355-2373.
18. Sullivan William J and Victoria Jeffers. “Mechanisms of Toxoplasma gondii persistence and latency”. FEMS Microbiology Reviews3 (2012): 717-33.
19. Nayeri Tooran., et al. “Effective factors in the pathogenesis of Toxoplasmagondii”. Heliyon10 (2024): e31558.
20. Dubey JP., et al. “Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts”. Clinical Microbiology Reviews2 (1998): 267-299.
21. McFadden Geoffrey Ian and Ellen Yeh. “The apicoplast: now you see it, now you don't”. International Journal for Parasitology2-3 (2017): 137-144.
22. Kim Kami. “A Bradyzoite is a Bradyzoite is a Bradyzoite?”. Trends in Parasitology12 (2015): 610-612.
23. Cerutti Aude., et al. “The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis”. Pathogens (Basel, Switzerland)3 (2020): 234.
24. Dubey JP. “Unexpected oocyst shedding by cats fed Toxoplasma gondii tachyzoites: in vivo stage conversion and strain variation”. Veterinary Parasitology4 (2005): 289-298.
25. Kidaka Taishi., et al. “TSS-seq of Toxoplasma gondii sporozoites revealed a novel motif in stage-specific promoters”. Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases 98 (2022): 105213.
26. Poukchanski Anna., et al. “Toxoplasma gondii sporozoites invade host cells using two novel paralogues of RON2 and AMA1”. PloS One8 (2013): e70637.
27. Morrissette Naomi S and L David Sibley. “Cytoskeleton of apicomplexan parasites”. Microbiology and Molecular Biology Reviews: MMBR1 (2002): 21-38.
28. Pasquarelli Rebecca R., et al. “Characterization and functional analysis of ToxoplasmaGolgi-associated proteins identified by proximity labeling”. mBio11 (2024): e0238024.
29. Dubremetz Jean François and Maryse Lebrun. "Virulence factors of Toxoplasma gondii”. Microbes and Infection15 (2012): 1403-1410.
30. Arisue Nobuko and Tetsuo Hashimoto. "Phylogeny and evolution of apicoplasts and apicomplexan parasites”. Parasitology International3 (2015): 254-259.
31. Whitelaw Jamie A., et al. “Surface attachment, promoted by the actomyosin system of Toxoplasma gondii is important for efficient gliding motility and invasion”. BMC Biology1 (2017): 1.
32. Katris Nicholas J., et al. “The apical complex provides a regulated gateway for secretion of invasion factors in Toxoplasma”. PLoS Pathogens4 (2014): e1004074.
33. Shen Bang and L David Sibley. “The moving junction, a key portal to host cell invasion by apicomplexan parasites”. Current Opinion in Microbiology4 (2012): 449-455.
34. Goldberg Daniel E and Joshua Zimmerberg. “Hardly Vacuous: The Parasitophorous Vacuolar Membrane of Malaria Parasites”. Trends in Parasitology2 (2020): 138-146.
35. Sanchez Syrian G and Sébastien Besteiro. “The pathogenicity and virulence of Toxoplasma gondii”. Virulence1 (2021): 3095-3114.
36. Portes Juliana., et al. “Toxoplasma gondiiMechanisms of Entry Into Host Cells”. Frontiers in Cellular and Infection Microbiology 10  (2020): 294.
37. Menard Kayla L., et al. “Impact of Toxoplasma gondiiInfection on Host Non-coding RNA Responses”. Frontiers in Cellular and Infection Microbiology 9  (2019): 132.
38. Zhao Xiao-Yu and Sarah E. Ewald. "The molecular biology and immune control of chronic Toxoplasma gondii infection”. The Journal of Clinical Investigation7 (2020): 3370-3380.v
39. Hakimi Mohamed-Ali., et al. “ToxoplasmaEffectors Targeting Host Signaling and Transcription”. Clinical Microbiology Reviews3 (2017): 615-645.
40. Montoya Jose G and Jack S Remington. "Toxoplasma gondii”. In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by John E. Bennett., et al., 9^th, Elsevier (2020): 3503-3520.
41. Robert-Gangneux Florence., et al. “New Molecular Diagnostic Tools for the Diagnosis of Maternal and Congenital Toxoplasmosis: Perspectives for 2030”. Microorganisms9 (2022): 1737.
42. Pomares Christelle and Pierre-Yves Levy. "Toxoplasmosis and Transplantation”. Transplant Infectious Disease3 (2020): e13213.
43. McAuley James B. "Congenital Toxoplasmosis”. Journal of the Pediatric Infectious Diseases Society1 (2014): S30-S35.
44. Halonen Sandra K and John P Weiss. "Toxoplasmosis”. Handbook of Clinical Neurology 114 (2013): 125-145.
45. Dunay Ian R., et al. “Toxoplasma gondii and Neurodegeneration”. Trends in Parasitology4 (2018): 261-272.
46. Villard O., et al. “Serological diagnosis of Toxoplasma gondii infection: Recommendations from the French National Reference Center for Toxoplasmosis”. Diagnostic Microbiology and Infectious Disease1 (2016): 22-33.
47. Switaj K., et al. “Recent trends in molecular diagnostics for Toxoplasma gondii infections”. Clinical Microbiology and Infection : The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases3 (2005): 170-176.
48. Hill D and J P Dubey. “Toxoplasma gondii: transmission, diagnosis and prevention”. Clinical Microbiology and Infection : The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases10 (2002): 634-640.
49. Müller Joachim and Andrew Hemphill. “Toxoplasma gondiiinfection: novel emerging therapeutic targets”. Expert Opinion on Therapeutic Targets4-5 (2023): 293-304.
50. Müller Joachim and Andrew Hemphill. “Toxoplasma gondii infection: novel emerging therapeutic targets”. Expert Opinion on Therapeutic Targets4-5 (2023): 293-304.
51. Anghel N., et al. “Endochin-like quinolones (ELQs) and bumped kinase inhibitors (BKIs): Synergistic and additive effects of combined treatments against Neospora caninum infection in vitro and in vivo”. International Journal for Parasitology: Drugs and Drug Resistance 17 (2021): 92-106.
52. Mévélec Marie-Noëlle., et al. “Key Limitations and New Insights Into the Toxoplasma gondiiParasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats”. Frontiers in Cellular and Infection Microbiology 10  (2020): 607198.
53. Assolini João Paulo., et al. “Nanomedicine advances in toxoplasmosis: diagnostic, treatment, and vaccine applications”. Parasitology Research116 (2017): 1603-1615.
54. Doggett J Stone., et al. “Bumped kinase inhibitor 1294 treats established Toxoplasma gondii infection”. Antimicrobial Agents and Chemotherapy6 (2014): 3547-3549.
55. Al Nasr., et al. “Toxoplasmosis and anti-Toxoplasma effects of medicinal plant extracts-A mini-review”. Asian Pacific Journal of Tropical Medicine8 (2016): 730-734.

Citation

Citation: Chandan S., et al. “Pathogenic Insights into Toxoplasma gondii: Host Interaction, Immune Evasion, and Therapeutic Strategies". Acta Scientific Veterinary Sciences 7.8 (2025): 27-40.

Copyright

Copyright: © 2025 Chandan S., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.