Athan C Baillet1, Linda M Rehaume1, Helen Benham1, Connor P O'Meara2, Charles W Armitage2, Roland Ruscher1, Geraldine Brizard3, Marina C G Harvie2, Jared Velasco1, Phillip M Hansbro4, John V Forrester5, Mariapia A Degli-Esposti6, Kenneth W Beagley2, Ranjeny Thomas1. 1. University of Queensland Diamantina Institute, Translational Research Institute and Princess Alexandra Hospital, Brisbane, Queensland, Australia. 2. Queensland University of Technology, Brisbane, Queensland, Australia. 3. Lions Eye Institute, Nedlands, West Australia, Australia. 4. Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia. 5. Lions Eye Institute, Nedlands, West Australia, Australia, and University of Aberdeen Medical School, Aberdeen, Scotland. 6. Lions Eye Institute, Nedlands, West Australia, Australia, and University of West Australia, Crawley, West Australia, Australia.
Abstract
OBJECTIVE: Chlamydia trachomatis 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(W163C) -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 Chlamydia muridarum in SKG mice and BALB/c mice. METHODS: After genital or respiratory infection with C muridarum, 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. RESULTS: Five weeks after vaginal infection with live C muridarum, 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 C muridarum 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. CONCLUSION: In the susceptible SKG strain, Chlamydia-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.
OBJECTIVE:Chlamydia trachomatis 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(W163C) -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 Chlamydia muridarum in SKG mice and BALB/c mice. METHODS: After genital or respiratory infection with C muridarum, 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. RESULTS: Five weeks after vaginal infection with live C muridarum, 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 C muridarum 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. CONCLUSION: In the susceptible SKG strain, Chlamydia-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.
Authors: Vidya Ranganathan; Eric Gracey; Matthew A Brown; Robert D Inman; Nigil Haroon Journal: Nat Rev Rheumatol Date: 2017-04-27 Impact factor: 20.543
Authors: Helga Raquel Garcia Ferrer; Alexander Azan; Isa Iraheta; Joan Von Feldt; Luis R Espinoza; Julia Manasson; Jose U Scher; Abraham Garcia Kutzbach; Alexis Ogdie Journal: Clin Rheumatol Date: 2017-11-14 Impact factor: 2.980
Authors: Tom Van de Wiele; Jens T Van Praet; Massimo Marzorati; Michael B Drennan; Dirk Elewaut Journal: Nat Rev Rheumatol Date: 2016-06-16 Impact factor: 20.543
Authors: Daniel B Horton; Brian L Strom; Mary E Putt; Carlos D Rose; David D Sherry; Julia S Sammons Journal: JAMA Pediatr Date: 2016-07-05 Impact factor: 16.193
Authors: Charlie Bridgewood; Abdulla Watad; Tobias Russell; Timothy M Palmer; Helena Marzo-Ortega; Almas Khan; Peter A Millner; Robert Dunsmuir; Abhay Rao; Peter Loughenbury; Miriam Wittmann; Richard J Cuthbert; Dennis G McGonagle Journal: Ann Rheum Dis Date: 2019-04-24 Impact factor: 19.103
Authors: Michael D Kruppa; Jeremy Jacobs; Kelsey King-Hook; Keleigh Galloway; Amy Berry; Jennifer Kintner; Judy D Whittimore; Rolf Fritz; Robert V Schoborg; Jennifer V Hall Journal: Front Microbiol Date: 2019-01-14 Impact factor: 5.640