IL-17A-mediated neutrophil recruitment limits expansion of segmented filamentous bacteria

• Authors: Kyle L. Flannigan, Georgia State University; Vu L. Ngo, Georgia State University; Duke Geem, Georgia State University; Akihito Harusato, Georgia State University; Simon A. Hirota, University of Calgary; Charles Parkos, Emory University; Nicholas W. Lukacs, University of Michigan; Asma Nusrat, Emory University; Valerie Gaboriau-Routhiau, University of Paris 05; Nadine Cerf-Bensussan, University of Paris 05; Andrew Gewirtz, Emory University; Timothy L. Denning, Georgia State University
• Journal Title: Mucosal Immunology
• Volume: Volume 10, Number 3
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals | 2017-05-01, Pages 673-684
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/mi.2016.80
• Subjects: Health Sciences, Immunology; Health Sciences, Pharmacology; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; T-CELL RESPONSES; IMMUNE-SYSTEM; INTESTINAL INFLAMMATION; GUT MICROBIOTA; TH17 RESPONSES; HOST-DEFENSE; INTERLEUKIN-17; DIFFERENTIATION; INNATE; IL-22

Abstract

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.