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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adoptive Transfer
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Animals
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Autoimmunity
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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Cell Line
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Cell Proliferation
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Chemokines / metabolism
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Chronic Pain / immunology*
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Chronic Pain / metabolism
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Chronic Pain / microbiology*
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Escherichia coli Infections / immunology
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Escherichia coli Infections / metabolism
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Gene Expression Regulation / immunology
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Gene Knockout Techniques
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Humans
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Interferon-gamma / deficiency
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Interleukin-17 / metabolism
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Male
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Mice
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Pelvic Pain / immunology*
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Pelvic Pain / metabolism
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Pelvic Pain / microbiology*
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Prostate / immunology
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Rats
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Species Specificity
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th17 Cells / immunology*
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Th17 Cells / metabolism
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Up-Regulation
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Urinary Tract Infections / immunology
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Urinary Tract Infections / metabolism
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Uropathogenic Escherichia coli / physiology*
Substances
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Chemokines
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Interleukin-17
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Interferon-gamma