The role of host autophagy machinery in controllingToxoplasmainfection

Abstract

Toxoplasma gondii is an obligate intracellular parasitic protist that infects a wide range of warm-blooded vertebrates. Although this parasite can cause serious complications, infections are often asymptomatic, allowing T. gondii to persist in its host and possibly enhancing the chances of its transmission. T. gondii has thus evolved multiple mechanisms of host manipulation to establish chronic infection. This persistence involves a balance between host immunity and parasite evasion of this immune response. This review highlights recent investigations that have demonstrated the important role played by the autophagy machinery in this balance, both in parasite control by the host, and in host exploitation by the parasite.

4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages

“…Accumulating evidence suggests that selective autophagy, also known as xenophagy, helps protect the host against diverse infectious agents including bacteria, viruses, and protozoa [7,8]. During T. gondii infection, the host's autophagy machinery contributes to the restriction of intracellular survival by maintaining a balance between the host immune response and exploitation of the host by the parasite [9].…”

Autophagy in the control and pathogenesis of parasitic infections

“…Macroautophagy, simply referred to as "autophagy" is known to be the most common autophagic process. It depends on the buildup of the double-membrane structure, autophagosome, that engulfs pathogens and further links to lysosomes for degradation [17,18]. The conservation of autophagy spans from yeast to mammals and is driven by autophagosome.…”

“…The conservation of autophagy spans from yeast to mammals and is driven by autophagosome. Autophagy is significantly known for providing alternative source of energy in response to starvation, also, it functions as a housekeeper in clearing unwanted proteins and damaged organelles [17,19]. Furthermore, autophagy clears pathogens by xenophagy [20,21].…”

“…The ATGs are reduced in Plasmodium and Toxoplasma, the two main protozoan parasites, despite the evolutionary conservation of the machinery for autophagy in most of the eukaryotic organisms. The ATG genes regulate the autophagic process, by triggering the formation of a double-membrane phagophore responsible for engulfing targeted pathogens and organelles [17]. This is coordinated by the Target Of Rapamycin (TOR) complex, acting as an inhibitor [17,30], and the class III phosphatidylinositol 3-kinase (PI3K) complex, playing a role as a regulator [17,31].…”

“…The ATG genes regulate the autophagic process, by triggering the formation of a double-membrane phagophore responsible for engulfing targeted pathogens and organelles [17]. This is coordinated by the Target Of Rapamycin (TOR) complex, acting as an inhibitor [17,30], and the class III phosphatidylinositol 3-kinase (PI3K) complex, playing a role as a regulator [17,31]. Since Apicomplexan parasites lack lysosomes, the parasite load in vacuoles is degraded with a proteolytic function [32].…”