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Science. 2017 Sep 8;357(6355):1047-1052. doi: 10.1126/science.aal4677. Epub 2017 Jul 27.

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

Author information

1
Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2
Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3
Broad Institute, Cambridge, MA 02142, USA.
4
Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
5
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02142, USA.
6
Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. lora.hooper@utsouthwestern.edu.
7
The Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

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.

Comment in

PMID:
28751470
PMCID:
PMC5702267
DOI:
10.1126/science.aal4677
[Indexed for MEDLINE]
Free PMC Article

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