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Toxoplasma gondii infection and its implications within the central nervous system

Nature Reviews Microbiology volume 19, pages 467–480 (2021)Cite this article

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Abstract

Toxoplasma gondii is a parasite that infects a wide range of animals and causes zoonotic infections in humans. Although it normally only results in mild illness in healthy individuals, toxoplasmosis is a common opportunistic infection with high mortality in individuals who are immunocompromised, most commonly due to reactivation of infection in the central nervous system. In the acute phase of infection, interferon-dependent immune responses control rapid parasite expansion and mitigate acute disease symptoms. However, after dissemination the parasite differentiates into semi-dormant cysts that form within muscle cells and neurons, where they persist for life in the infected host. Control of infection in the central nervous system, a compartment of immune privilege, relies on modified immune responses that aim to balance infection control while limiting potential damage due to inflammation. In response to the activation of interferon-mediated pathways, the parasite deploys an array of effector proteins to escape immune clearance and ensure latent survival. Although these pathways are best studied in the laboratory mouse, emerging evidence points to unique mechanisms of control in human toxoplasmosis. In this Review, we explore some of these recent findings that extend our understanding for proliferation, establishment and control of toxoplasmosis in humans.

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Fig. 1: Dissemination of acute and establishment of chronic Toxoplasma gondii infection.
Fig. 2: Toxoplasma gondii differentiation and migration into the central nervous system.
Fig. 3: Differences in murine and human cell autonomous control.
Fig. 4: Modulation of host cellular immune pathways by Toxoplasma gondii effectors.

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Acknowledgements

This work is supported in part by a grant from the National Institutes of Health (NIH) (AI188426).

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Authors and Affiliations

  1. Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA

    Sumit K. Matta, Nicholas Rinkenberger & L. David Sibley

  2. Institute of Inflammation and Neurodegeneration, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    Ildiko R. Dunay

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Contributions

S.K.M, N.R. and I.R.D. researched data for the article. All authors substantially contributed to discussion of content. The authors contributed equally to all other aspects of the article. S.K.M, I.R.D. and L.D.S. wrote the article. L.D.S. reviewed/edited the manuscript before submission.

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Correspondence to L. David Sibley.

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Glossary

Apicomplexan parasite

Protozoa in the phylum Apicomplexa are largely intracellular parasites that utilize distinctive and complex structures at their apical end to invade and replicate within a host cell.

Enterocytes

Cells that line the small and large intestine in vertebrates and are involved in absorption of nutrients.

Ileitis

Inflammation of the ileum that occurs as a common symptom of toxoplasmosis in mice and many other hosts.

Immune privilege

Refers to tissue compartments that show reduced immune responsiveness and inflammation in response to foreign antigens. It is considered an adaptation to maintain the tissue architecture critical for host survival. Examples include the central nervous system, eyes, placenta and fetus.

Parenchyma

The main brain tissue that is composed of neurons and glial cells.

Cre-recombinase

A P1 bacteriophage recombinase that catalyses DNA recombination at sites containing 34-bp LoxP recognition sites.

Dendritic spines

Cellular protrusions along neuronal dendrites that form excitatory synapses.

Phagophore membrane

A double-membrane vacuole synthesized de novo by the autophagy initiation complex. It eventually matures into an autophagosome to execute the process of autophagy in cell.

Xenophagy

A cellular process of engulfing intracellular pathogens in large, double membrane-bound autophagic vacuole.

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Matta, S.K., Rinkenberger, N., Dunay, I.R. et al. Toxoplasma gondii infection and its implications within the central nervous system. Nat Rev Microbiol 19, 467–480 (2021). https://doi.org/10.1038/s41579-021-00518-7

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