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Nat Immunol. 2015 Sep;16(9):918-26. doi: 10.1038/ni.3233. Epub 2015 Aug 3.

Commensal bacteria direct selective cargo sorting to promote symbiosis.

Author information

1
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
2
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
3
1] Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. [2] CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences, Beijing, China.

Abstract

Mucosal immunity protects a host from intestinal inflammation and infection and is profoundly influenced by symbiotic bacteria. Here we report that in mice symbiotic bacteria directed selective cargo sorting in Paneth cells to promote symbiosis through Nod2, a cytosolic bacterial sensor, and the multifunctional protein kinase LRRK2, both encoded by inflammatory bowel disease (IBD)-associated genes. Commensals recruited Nod2 onto lysozyme-containing dense core vesicles (DCVs), which was required for DCV localization of LRRK2 and a small GTPase, Rab2a. Deficiency of Nod2, LRRK2 or Rab2a or depletion of commensals resulted in lysosomal degradation of lysozyme. Thus, commensal bacteria and host factors orchestrate the lysozyme-sorting process to protect the host from enteric infection, implicating Paneth cell dysfunction in IBD pathogenesis.

PMID:
26237551
DOI:
10.1038/ni.3233
[Indexed for MEDLINE]

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