BCL2 regulates antibacterial autophagy in the intestinal epithelium.

Autor:	Li Y; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390., Bel S; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390., Benjamin JL; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390., Ruhn KA; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390., Hassell B; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390., Behrendt CL; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390., Kuang Z; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390., Hooper LV; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390.; HHMI, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Dec 03; Vol. 121 (49), pp. e2410205121. Date of Electronic Publication: 2024 Nov 27.
DOI:	10.1073/pnas.2410205121
Abstrakt:	Autophagy is a key innate immune defense mechanism in intestinal epithelial cells. Bacterial invasion of epithelial cells activates antibacterial autophagy through a process that requires the innate immune adaptor protein MYD88, yet how MYD88 signaling connects to the autophagy machinery is unknown. Here, we show that the mouse intestinal pathogen Salmonella enterica Serovar Typhimurium ( Salmonella Typhimurium) triggers MYD88 signaling that regulates binding of the anti-autophagy factor B cell lymphoma 2 (BCL2) to the essential autophagy protein Beclin1 (BECN1) in small intestinal enterocytes, a key epithelial cell lineage. Salmonella infection activated the kinase c-Jun N-terminal protein kinase 1 (JNK1) downstream of MYD88. JNK1 induced enterocyte BCL2 phosphorylation, promoting dissociation of the inhibitory BCL2-BECN1 complex and releasing BECN1 to initiate autophagy. Mice with BCL2 phosphorylation site mutations that prevent BCL2-BECN1 dissociation showed increased Salmonella invasion of enterocytes and dissemination to extraintestinal sites. These findings reveal that BCL2 links MYD88 signaling to enterocyte autophagy initiation, providing mechanistic insight into how invading bacteria trigger autophagy in the intestinal epithelium. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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