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Choi, Jayoung; Park, Sunmin; Biering, Scott B.; Selleck, Elizabeth; Liu, Catherine Y.; Zhang, Xin; Fujita, Naonobu; Saitoh, Tatsuya; Akira, Shizuo; Yoshimori, Tamotsu; Sibley, L. David; Hwang, Seungmin; Virgin, Herbert W.
Immunity, 06/2014, Letnik: 40, Številka: 6Journal Article
Autophagy is a lysosomal degradation pathway that is important in cellular homeostasis. Prior work showed a key role for the autophagy related 5 (Atg5) in resistance to Toxoplasma gondii. Here we show that the cassette of autophagy proteins involved in the conjugation of microtubule-associated protein 1 light chain 3 (LC3) to phosphatidylethanolamine, including Atg7, Atg3, and the Atg12-Atg5-Atg16L1 complex play crucial roles in the control of T. gondii in vitro and in vivo. In contrast, pharmacologic modulation of the degradative autophagy pathway or genetic deletion of other essential autophagy genes had no substantial effects. Rather the conjugation system was required for targeting of LC3 and interferon-γ effectors onto the vacuolar membrane of T. gondii and its consequent disruption. These data suggest that the ubiquitin-like conjugation systems that reorganize intracellular membranes during canonical autophagy are necessary for proper targeting of immune effectors to the intracellular vacuole membranes utilized by pathogens. Display omitted •A cassette of Atg7, Atg3, Atg12-Atg5-Atg16L1 mediates IFN-γ control of T. gondii•The degradative pathway of autophagy is not required for IFN-γ control of T. gondii•Autophagy proteins mark membrane structures by pathogens for intracellular immunity•Autophagy proteins are required to direct IFN-γ effectors to membranes of pathogens Autophagy is an evolutionarily conserved lysosomal degradative process important for host defense and cellular homeostasis. Choi et al. show that a cassette of autophagy proteins involved in ubiquitin-like conjugation reactions functions, independent of degradative activity, in host defense.
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