A TNF-α-CCL20-CCR6 axis regulates Nod1-induced B cell responses

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....

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Published in:	The Journal of immunology (1950) Vol. 192; no. 6; pp. 2787 - 2799
Main Authors:	Paradis, Maude, Mindt, Barbara C, Duerr, Claudia U, Rojas, Olga L, Ng, Dennis, Boulianne, Bryant, McCarthy, Doug D, Yu, Mingxi Dennis, Summers deLuca, Leslie E, Ward, Lesley A, Waldron, James B, Philpott, Dana J, Gommerman, Jennifer L, Fritz, Jörg H
Format:	Journal Article
Language:	English
Published:	United States 15-03-2014
Subjects:	Animals B-Lymphocytes - drug effects B-Lymphocytes - immunology B-Lymphocytes - metabolism Bone Marrow Cells - drug effects Bone Marrow Cells - immunology Bone Marrow Cells - metabolism Bone Marrow Transplantation - methods Cell Line Cells, Cultured Chemokine CCL20 - immunology Chemokine CCL20 - metabolism Diaminopimelic Acid - analogs & derivatives Diaminopimelic Acid - pharmacology Female Flow Cytometry Lymphocyte Count Lymphoid Tissue - cytology Lymphoid Tissue - immunology Lymphoid Tissue - metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Fluorescence Neutrophils - drug effects Neutrophils - immunology Neutrophils - metabolism Nod1 Signaling Adaptor Protein - genetics Nod1 Signaling Adaptor Protein - immunology Nod1 Signaling Adaptor Protein - metabolism Receptors, CCR6 - genetics Receptors, CCR6 - immunology Receptors, CCR6 - metabolism Spleen - cytology Spleen - immunology Spleen - metabolism Transplantation Chimera - blood Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - immunology Tumor Necrosis Factor-alpha - metabolism
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.1203310