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PMID: 26237551 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Commensal bacteria direct selective cargo sorting to promote symbiosis.

Nature immunology ·Vol. 16 ·No. 9 ·2015-09-00 ·Pages 918-26

Zhang Q, Pan Y, Yan R, Zeng B, Wang H, Zhang X, Li W, Wei H, Liu Z

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.

MeSH Terms
Animals Enterocolitis/genetics,immunology Immunity, Mucosal/genetics,immunology Inflammatory Bowel Diseases/genetics,immunology Intestines/immunology,microbiology Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Listeriosis/genetics,immunology Lysosomes Mice Mice, Knockout Muramidase Nod2 Signaling Adaptor Protein/genetics,immunology Paneth Cells/immunology Protein Serine-Threonine Kinases/genetics,immunology Secretory Vesicles/immunology Symbiosis/genetics,immunology rab GTP-Binding Proteins/genetics,immunology
Chemicals
Nod2 Signaling Adaptor Protein Nod2 protein, mouse Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Lrrk2 protein, mouse Protein Serine-Threonine Kinases Muramidase Rab2a protein, mouse rab GTP-Binding Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhang Qin
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Pan Ying
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Yan Ruiqing
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Zeng Benhua
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
Wang Haifang
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Zhang Xinwen
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Li Wenxia
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
Wei Hong
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
Liu Zhihua ORCID
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.
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.3233
Published
2015-09-00
Epub
2015-00-03
Pages
918-26
Language
English
Region
United States
NLM ID
100941354
Subset
IM
Corrections
CommentIn
PMID: 26287588
External Links
PubMed source DOI: 10.1038/ni.3233 View journal details
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