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

Shai Bel, Mihir Pendse, Yuhao Wang, Yun Li, Kelly A. Ruhn, Brian Hassell, Tess Leal, Sebastian E. Winter, Ramnik J. Xavier, Lora V. Hooper

Research output: Contribution to journalArticlepeer-review

242 Scopus citations

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.

Original languageEnglish
Pages (from-to)1047-1052
Number of pages6
JournalScience
Volume357
Issue number6355
DOIs
StatePublished - 8 Sep 2017
Externally publishedYes

Bibliographical note

Funding Information:
We thank B. Levine for discussions and C. L. Behrendt-Boyd for assistance with mouse experiments. This work was supported by the NIH (grant DK070855 to L.V.H.; grants AI118807 and AI128151 to S.E.W.), the Burroughs Wellcome Foundation (Investigators in the Pathogenesis of Infectious Diseases Award to L.V.H.), the Welch Foundation (grant I-1874 to L.V.H.; grant I-1858 to S.E.W.), and the Howard Hughes Medical Institute (L.V.H.). S.B. was supported by a Gruss-Lipper postdoctoral fellowship.

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