A role for the pattern recognition receptor Nod2 in promoting recruitment of CD103+ dendritic cells to the colon in response to Trichuris muris infection.
The ability of the colon to generate an immune response to pathogens, such as the model pathogen Trichuris muris, is a fundamental and critical defense mechanism. Resistance to T. muris infection is associated with the rapid recruitment of dendritic cells (DCs) to the colonic epithelium via epithelial chemokine production. However, the epithelial-pathogen interactions that drive chemokine production are not known. We addressed the role of the cytosolic pattern recognition receptor Nod2. In response to infection, there was a rapid influx of CD103(+)CD11c(+) DCs into the colonic epithelium in wild-type (WT) mice, whereas this was absent in Nod2(-/-) animals. In vitro chemotaxis assays and in vivo experiments using bone marrow chimeras of WT mice reconstituted with Nod2(-/-) bone marrow and infected with T. muris demonstrated that the migratory function of Nod2(-/-) DCs was normal. Investigation of colonic epithelial cell (CEC) innate responses revealed a significant reduction in epithelial production of the chemokines CCL2 and CCL5 but not CCL20 by Nod2-deficient CECs. Collectively, these data demonstrate the importance of Nod2 in CEC responses to infection and the requirement for functional Nod2 in initiating host epithelial chemokine-mediated responses and subsequent DC recruitment and T-cell responses following infection.
1] Faculty of Life Sciences, University of Manchester, Manchester, UK [2] Present address: Department of Microbiology, New York University, New York, USA.
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R
Bowcutt
Faculty of Life Sciences, University of Manchester, Manchester, UK.
M
M
Bramhall
Faculty of Life Sciences, University of Manchester, Manchester, UK.
L
L
Logunova
Epistem, Manchester, UK.
J
J
Wilson
Epistem, Manchester, UK.
C
C
Booth
Gut Health and Food Safety Research Programme, Institute of Food Research and the Norwich Medical School, University of East Anglia, Norwich, UK.
S R
SR
Carding
Faculty of Life Sciences, University of Manchester, Manchester, UK.
R
R
Grencis
Faculty of Life Sciences, University of Manchester, Manchester, UK.
S
S
Cruickshank
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D003106:Colon / Q000276:immunology* / Q000469:parasitology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055786:Gene Knockout Techniques; D039001:Integrin alpha Chains / Q000378:metabolism*; D008297:Male; D051379:Mice; D009349:Nematode Infections / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D014258:Trichuris / Q000276:immunology*
D015703:Antigens, CD; D039001:Integrin alpha Chains; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C091367:alpha E integrins