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Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine

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Science  08 Sep 2017:
Vol. 357, Issue 6355, pp. 1047-1052
DOI: 10.1126/science.aal4677

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Foiling bad bugs' sneaky tricks

Intestinal pathogens can invade host cells and disrupt critical cellular functions, including secretion. Secretion is necessary for the delivery of antimicrobial proteins that kill pathogenic bacteria. Bel et al. show that when intestinal epithelial cells sense an invading bacterial pathogen, they “reroute” the antimicrobial protein lysozyme through an alternative autophagy-based secretion pathway (see the Perspective by Kaser and Blumberg). This ensures lysozyme delivery to the gut lumen, which protects against further bacterial invasion. Secretory autophagy was triggered by endoplasmic reticulum stress and required signals from type 3 innate lymphoid cells. Thus, the innate immune response to gut pathogens co-opts autophagy in intestinal immune defense.

Science, this issue p. 1047; see also p. 976

Abstract

Intestinal Paneth cells limit bacterial invasion by secreting antimicrobial proteins, including lysozyme. However, invasive pathogens can disrupt the Golgi apparatus, interfering with secretion and compromising intestinal antimicrobial defense. Here we show that during bacterial infection, lysozyme is rerouted via secretory autophagy, an autophagy-based alternative secretion pathway. Secretory autophagy was triggered in Paneth cells by bacteria-induced endoplasmic reticulum (ER) stress, required extrinsic signals from innate lymphoid cells, and limited bacterial dissemination. Secretory autophagy was disrupted in Paneth cells of mice harboring a mutation in autophagy gene Atg16L1 that confers increased risk for Crohn’s disease in humans. Our findings identify a role for secretory autophagy in intestinal defense and suggest why Crohn’s disease is associated with genetic mutations that affect both the ER stress response and autophagy.

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