title: Interleukin-22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice.
abstract: Our previous work has shown the significant up-regulation of Il22 and increased phosphorylation of signal transducer and activator of transcription 3 (STAT3) as part of the mucosal inflammatory response to Clostridium difficile infection in mice. Others have shown that phosphorylation of STAT3 at mucosal surfaces includes interleukin-22 (IL-22) and CD160-mediated components. The current study sought to determine the potential role(s) of IL-22 and/or CD160 in the mucosal response to C. difficile infection. Clostridium difficile-infected mice treated with anti-IL-22, anti-CD160 or a combination of the two showed significantly reduced STAT3 phosphorylation in comparison to C. difficile-infected mice that had not received either antibody. In addition, C. difficile-infected mice treated with anti-IL-22/CD160 induced a smaller set of genes, and at significantly lower levels than the untreated C. difficile-infected mice. The affected genes included pro-inflammatory chemokines and cytokines, and anti-microbial peptides. Furthermore, histopathological and flow cytometric assessments both showed a significantly reduced influx of neutrophils in C. difficile-infected mice treated with anti-IL-22/CD160. These data demonstrate that IL-22 and CD160 are together responsible for a significant fraction of the colonic STAT3 phosphorylation in C. difficile infection. They also underscore the additive effects of IL-22 and CD160 in mediating both the pro-inflammatory and pro-survival aspects of the host mucosal response in this infection.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Amir A
authors.initials: AA
authors.lastname: Sadighi Akha
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McDermott
authors.forename: Casey M
authors.initials: CM
authors.lastname: Theriot
authors.forename: Paul E
authors.initials: PE
authors.lastname: Carlson
authors.forename: Charles R
authors.initials: CR
authors.lastname: Frank
authors.forename: Roderick A
authors.initials: RA
authors.lastname: McDonald
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Falkowski
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Bergin
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
authors.forename: Gary B
authors.initials: GB
authors.lastname: Huffnagle
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016360:Clostridioides difficile / Q000276:immunology / Q000472:pathogenicity*; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D018928:Immunity, Mucosal / Q000187:drug effects; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D000097043:Interleukin-22
chemical_list: D000900:Anti-Bacterial Agents; D000906:Antibodies; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D007378:Interleukins; D011971:Receptors, Immunologic; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C511585:Cd160 protein, mouse; C494087:Stat3 protein, mouse
keywords: CD160; Clostridium difficile; RegIIIγ; interleukin-22; pSTAT3