Autophagy gene-dependent intracellular immunity triggered by interferon-γ.

Autor:	McAllaster MR; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.; Vir Biotechnology, San Francisco, California, USA., Bhushan J; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA., Balce DR; Vir Biotechnology, San Francisco, California, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA., Orvedahl A; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA., Park A; Vir Biotechnology, San Francisco, California, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA., Hwang S; Vir Biotechnology, San Francisco, California, USA., Sullender ME; Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA., Sibley LD; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA., Virgin HW; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2023 Dec 19; Vol. 14 (6), pp. e0233223. Date of Electronic Publication: 2023 Oct 31.
DOI:	10.1128/mbio.02332-23
Abstrakt:	Importance: Interferon-γ (IFNγ) is a critical mediator of cell-intrinsic immunity to intracellular pathogens. Understanding the complex cellular mechanisms supporting robust interferon-γ-induced host defenses could aid in developing new therapeutics to treat infections. Here, we examined the impact of autophagy genes in the interferon-γ-induced host response. We demonstrate that genes within the autophagy pathway including Wipi2 , Atg9 , and Gate-16 , as well as ubiquitin ligase complex genes Cul3 and Klhl9 are required for IFNγ-induced inhibition of murine norovirus (norovirus hereinafter) replication in mouse cells. WIPI2 and GATE-16 were also required for IFNγ-mediated restriction of parasite growth within the Toxoplasma gondii parasitophorous vacuole in human cells. Furthermore, we found that perturbation of UFMylation pathway components led to more robust IFNγ-induced inhibition of norovirus via regulation of endoplasmic reticulum (ER) stress. Enhancing or inhibiting these dynamic cellular components could serve as a strategy to control intracellular pathogens and maintain an effective immune response. Competing Interests: D.R.B., M.R.M., A.P., S.H., and H.W.V. are employees of and hold stock in Vir Biotechnology, where some of the work was performed. D.R.B., M.R.M., A.P., and H.W.V. made the initial observations reported here while at Washington University School of Medicine in St. Louis without funding from Vir Biotechnology. H.W.V. is a founder of Casma Therapeutics and PiernianDx, neither of which funded the research reported herein. L.D.S. is a consultant for Kainomyx, which had no role in the study.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu