title: A TNF-α-CCL20-CCR6 axis regulates Nod1-induced B cell responses.
abstract: Innate immune responses provoke the accumulation of leukocytes at sites of inflammation. In addition to monocytes and granulocytes, B cells also participate in antimicrobial innate immune responses; however, the mechanisms for accumulation of B cells to sites of inflammation are not well understood. To study B cell accumulation following systemic inflammation, we used a model synthetic ligand that stimulates a specific pattern recognition molecule, nucleotide-binding oligomerization domain-containing protein 1 (Nod1). Upon exposure to Nod1 agonists, both B cells and neutrophils rapidly accumulate within the spleen, and dendritic cells migrate into the periarterial lymphoid sheath. Nod1 stimulation led to a marked increase in several chemokines within the spleen, including CXCL13, CCL2, and CCL20. Whereas the lymphotoxin pathway was critical for the induction of the B cell chemoattractant CXCL13 in response to Nod1 agonists, B cell accumulation within the spleen following Nod1-induced systemic inflammation was independent of the lymphotoxin pathway. In contrast, a CCR6/CCL20 chemokine loop instructed rapid increase of B cells in the spleen in response to systemic administration of Nod1 agonists in a TNF-α-dependent manner. Moreover, CCR6 was required to regulate Nod1-mediated B cell responses. These results reveal a novel mechanism of B cells during inflammation and shed light on how B cells participate in innate immune responses to microbial stimulation.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Complex Traits Group, Montreal, Quebec H3G 0B1, Canada;
authors.forename: Maude
authors.initials: M
authors.lastname: Paradis
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Mindt
authors.forename: Claudia U
authors.initials: CU
authors.lastname: Duerr
authors.forename: Olga L
authors.initials: OL
authors.lastname: Rojas
authors.forename: Dennis
authors.initials: D
authors.lastname: Ng
authors.forename: Bryant
authors.initials: B
authors.lastname: Boulianne
authors.forename: Doug D
authors.initials: DD
authors.lastname: McCarthy
authors.forename: Mingxi Dennis
authors.initials: MD
authors.lastname: Yu
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Summers deLuca
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Ward
authors.forename: James B
authors.initials: JB
authors.lastname: Waldron
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gommerman
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Fritz
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D002460:Cell Line; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000276:immunology* / Q000378:metabolism; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054399:Receptors, CCR6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018183:Transplantation Chimera / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D054399:Receptors, CCR6; D014409:Tumor Necrosis Factor-alpha; D003960:Diaminopimelic Acid; C034330:FK 156