title: Commensal bacteria direct selective cargo sorting to promote symbiosis.
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.
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Benhua
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Haifang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Zhihua
authors.identifier: 0000000202690901
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D004760:Enterocolitis / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000235:genetics / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D008247:Lysosomes; D051379:Mice; D018345:Mice, Knockout; D009113:Muramidase; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology; D019879:Paneth Cells / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*; D022142:Secretory Vesicles / Q000276:immunology; D013559:Symbiosis / Q000235:genetics / Q000276:immunology*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D020693:rab2 GTP-Binding Protein
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009113:Muramidase; D053473:Nod2 Signaling Adaptor Protein; D017346:Protein Serine-Threonine Kinases; D020691:rab GTP-Binding Proteins; C495945:Nod2 protein, mouse; C495279:Lrrk2 protein, mouse; C000602046:Rab2a protein, mouse; D020693:rab2 GTP-Binding Protein