title: Th1-Th17 cells contribute to the development of uropathogenic Escherichia coli-induced chronic pelvic pain.
abstract: The etiology of chronic prostatitis/chronic pelvic pain syndrome in men is unknown but may involve microbes and autoimmune mechanisms. We developed an infection model of chronic pelvic pain in NOD/ShiLtJ (NOD) mice with a clinical Escherichia coli isolate (CP-1) from a patient with chronic pelvic pain. We investigated pain mechanisms in NOD mice and compared it to C57BL/6 (B6) mice, a strain resistant to CP-1-induced pain. Adoptive transfer of CD4+ T cells, but not serum, from CP-1-infected NOD mice was sufficient to induce chronic pelvic pain. CD4+ T cells in CP-1-infected NOD mice expressed IFN-γ and IL-17A but not IL-4, consistent with a Th1/Th17 immune signature. Adoptive transfer of ex-vivo expanded IFN-γ or IL-17A-expressing cells was sufficient to induce pelvic pain in naïve NOD recipients. Pelvic pain was not abolished in NOD-IFN-γ-KO mice but was associated with an enhanced IL-17A immune response to CP1 infection. These findings demonstrate a novel role for Th1 and Th17-mediated adaptive immune mechanisms in chronic pelvic pain.
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Marsha L
authors.initials: ML
authors.lastname: Quick
authors.forename: Larry
authors.initials: L
authors.lastname: Wong
authors.forename: Soumi
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Done
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Schaeffer
authors.forename: Praveen
authors.initials: P
authors.lastname: Thumbikat
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D059350:Chronic Pain / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D055786:Gene Knockout Techniques; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D051379:Mice; D017699:Pelvic Pain / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D011467:Prostate / Q000276:immunology; D051381:Rats; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D014552:Urinary Tract Infections / Q000276:immunology / Q000378:metabolism; D056689:Uropathogenic Escherichia coli / Q000502:physiology*
chemical_list: D018925:Chemokines; D020381:Interleukin-17; D007371:Interferon-gamma