High Chlamydia Burden Promotes Tumor Necrosis Factor–Dependent Reactive Arthritis in SKG Mice. Issue 6 (June 2015)

• Record Type: Journal Article
• Authors: Baillet, Athan C.; Rehaume, Linda M.; Benham, Helen; O'Meara, Connor P.; Armitage, Charles W.; Ruscher, Roland; Brizard, Geraldine; Harvie, Marina C. G.; Velasco, Jared; Hansbro, Phillip M.; Forrester, John V.; Degli‐Esposti, Mariapia A.; Beagley, Kenneth W.; Thomas, Ranjeny
• Is Part Of: Arthritis & rheumatology. Volume 67:Issue 6(2015)
• Page Start: 1535
• Page End: 1547
• Publication Date: 2015-06
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.39041
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art39041-sec-0001" sec-type="section"> <title>Objective</title> <p> <italic>Chlamydia trachomatis</italic> is a sexually transmitted obligate intracellular pathogen that causes inflammatory reactive arthritis, spondylitis, psoriasiform dermatitis, and conjunctivitis in some individuals after genital infection. The immunologic basis for this inflammatory response in susceptible hosts is poorly understood. As ZAP‐70<sup>W163C</sup>–mutant BALB/c (SKG) mice are susceptible to spondylo‐arthritis after systemic exposure to microbial β‐glucan, we undertook the present study to compare responses to infection with <italic>Chlamydia muridarum</italic> in SKG mice and BALB/c mice.</p> </sec> <sec id="art39041-sec-0002" sec-type="section"> <title>Methods</title> <p>After genital or respiratory infection with <italic>C muridarum</italic>, conjunctivitis and arthritis were assessed clinically, and eye, skin, and joint specimens were analyzed histologically. Chlamydial major outer membrane protein antigen–specific responses were assessed in splenocytes. Treg cells were depleted from FoxP3‐DTR BALB/c or SKG mice, and chlamydial DNA was quantified by polymerase chain reaction.</p> </sec> <sec id="art39041-sec-0003" sec-type="section"> <title>Results</title> <p>Five weeks after vaginal infection with live <italic>C muridarum</italic>, arthritis, spondylitis, and psoriasiform dermatitis developed in female SKG mice, but not in BALB/c mice. Inflammatory bowel disease did not occur in mice of either strain. The severity of inflammatory disease was correlated with <italic>C muridarum</italic> inoculum size and vaginal burden postinoculation. Treatment with combination antibiotics starting 1 day postinoculation prevented disease. Chlamydial antigen was present in macrophages and spread from the infection site to lymphoid organs and peripheral tissue. In response to chlamydial antigen, production of interferon‐γ and interleukin‐17 was impaired in T cells from SKG mice but tumor necrosis factor (TNF) responses were exaggerated, compared to findings in T cells from BALB/c mice. Unlike previous observations in arthritis triggered by β‐glucan, no autoantibodies developed. Accelerated disease triggered by depletion of Treg cells was TNF dependent.</p> </sec> <sec id="art39041-sec-0004" sec-type="section"> <title>Conclusion</title> <p>In the susceptible SKG strain, <italic>Chlamydia</italic>‐induced reactive arthritis develops as a result of deficient intracellular pathogen control, with antigen‐specific TNF production upon dissemination of antigen, and TNF‐dependent inflammatory disease.</p> </sec> </abstract>