IL-17A-mediated neutrophil recruitment limits expansion of segmented filamentous bacteria.
Specific components of the intestinal microbiota are capable of influencing immune responses such that a mutualistic relationship is established. In mice, colonization with segmented filamentous bacteria (SFB) induces T-helper-17 (Th17) cell differentiation in the intestine, yet the effector functions of interleukin (IL)-17A in response to SFB remain incompletely understood. Here we report that colonization of mice with SFB-containing microbiota induced IL-17A- and CXCR2-dependent recruitment of neutrophils to the ileum. This response required adaptive immunity, as Rag-deficient mice colonized with SFB-containing microbiota failed to induce IL-17A, CXCL1 and CXCL2, and displayed defective neutrophil recruitment to the ileum. Interestingly, neutrophil depletion in wild-type mice resulted in significantly augmented Th17 responses and SFB expansion, which correlated with impaired expression of IL-22 and antimicrobial peptides. These data provide novel insight into a dynamic IL-17A-CXCR2-neutrophil axis during acute SFB colonization and demonstrate a central role for neutrophils in limiting SFB expansion.
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.|Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
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Flannigan
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
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Ngo
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.|Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
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Geem
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
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Harusato
Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
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Hirota
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
C A
CA
Parkos
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
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Lukacs
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
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Nusrat
INSERM, U1163, Laboratory of Intestinal Immunity, Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, Paris, France.|Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
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Gaboriau-Routhiau
INSERM, U1163, Laboratory of Intestinal Immunity, Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, Paris, France.
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Cerf-Bensussan
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
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AT
Gewirtz
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
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Denning
D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D001419:Bacteria / Q000254:growth & development / Q000276:immunology*; D002454:Cell Differentiation; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D007082:Ileum / Q000276:immunology* / Q000382:microbiology; D020381:Interleukin-17 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology*; D000097043:Interleukin-22
D023181:Antimicrobial Cationic Peptides; D018398:Homeodomain Proteins; D020381:Interleukin-17; D007378:Interleukins; D023063:Receptors, Interleukin-8B; D000097043:Interleukin-22; C064658:RAG-1 protein