Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells During Toxoplasma gondii Infection and Potential Therapeutic Implications.

Carlos S Subauste

doi:10.3389/fcell.2021.673813

Carlos S Subauste

Open Access

https://doi.org/10.3389/fcell.2021.673813

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Abstract

Toxoplasma gondii is an obligate intracellular protozoan that can cause encephalitis and retinitis in humans. The success of T. gondii as a pathogen depends in part on its ability to form an intracellular niche (parasitophorous vacuole) that allows protection from lysosomal degradation and parasite replication. The parasitophorous vacuole can be targeted by autophagy or by autophagosome-independent processes triggered by autophagy proteins. However, T. gondii has developed many strategies to preserve the integrity of the parasitophorous vacuole. Here, we review the interaction between T. gondii, autophagy, and autophagy proteins and expand on recent advances in the field, including the importance of autophagy in the regulation of invasion of the brain and retina by the parasite. We discuss studies that have begun to explore the potential therapeutic applications of the knowledge gained thus far.

Highlights

Intracellular pathogens have developed a broad range of strategies to survive within host cells
T. gondii secretes proteins during its interaction with host cells that: (i) Enable the formation of a parasitophorous vacuole (PV) that avoids the classical pathway of phagolysosomal fusion; (ii) Activate host cell signaling cascades that negatively regulate autophagic targeting of the PV
The parasite avoids lysosomal degradation mediated by constitutive autophagy and prevents its complete eradication when autophagy is stimulated by CD40; (iii) Impair the ability of interferon-gamma (IFN-γ) to activate autophagosome-independent effector mechanisms directed against the PV

Summary

Introduction

Intracellular pathogens have developed a broad range of strategies to survive within host cells. The likely mechanisms of protection against cerebral and ocular toxoplasmosis identified in mice are as follows: (i) CD40-induced toxoplasmacidal activity in macrophages/microglia (Reichmann et al, 2000; Portillo et al, 2010); (ii) recently identified induction of toxoplasmacidal activity in neural endothelial cells accompanied by reduced invasion of the brain and retina by the parasite (Portillo et al, 2019); (iii) reduced anti-T. gondii antibody production (Portillo et al, 2021); (iv) protection against CD8+ T cell exhaustion (Bhadra et al, 2011).

Results

Conclusion