Reactive arthritis (ReA) is a chronic disease characterized by periods of flare alternating with periods of less active inflammation. One criterion of disease classification is a history of prior sexually transmitted or GI infection. Recent data from our collaborative group have shown that a significant number of ReA patients have metabolically active chlamydia in their synovial tissues. To facilitate study of ReA, we developed a murine model of genital chlamydial infection using a human strain of Chlamydia trachomatis to study the inflammatory/immunopathologic mechanisms of joint inflammation. Mice develop ascending genital infection within three weeks. Synovial tissue from knees of these animals exhibits histologic signs of synovitis including increased synovial lining cells, dilated vessels, and foci of mononuclear inflammatory cells, and is PCR positive for chlamydial genes. This model will extend our previous data from a murine ocular chlamydial infection model that demonstrated both dissemination of chlamydia to synovial tissue and development of synovitis.The model will allow us to test mechanisms in chlamydia-associated spondyloarthropathy (ReA) relating to the initiation of synovial inflammation and to determine the roles of local and distant host responses in development of persistent chlamydial infection. Specific molecular, microbiologic and immunologic questions to be asked with the murine model are guided by questions raised by the group's clinical findings from ReA patients: (1) what are the roles of pro-inflammatory and immunologic cytokines produced in synovial tissue during the inflammatory processes? (2) what host cells are infected and where does chlamydial persistence begin? (3) what is the metabolic state of chlamydia in those cells? (4) are persistently infected host cells (presumed mononuclear cells/macrophages) the stimulus for inflammation, or do responses by uninfected host cells to the latter provide the inflammatory stimulus? (5) do the locally produced cytokines determine the establishment of inapparent/persistent chlamydial infection in synovial tissue? The proposed studies in a noninvasive murine model of reactive arthritis will extend our clinical and laboratory findings from patients with chlamydia-associated reactive arthritis, and under controlled experimental conditions, enable us to determine the host cells vs chlamydial components which predispose to development and chronicity of joint inflammation. In the long term, these studies will lead to improved therapies for patients with reactive arthritis and/or indicate requirements to prevent this spondyloarthropathy.
| Gerard, Herve C; Stanich, Jessica A; Oszust, Cynthia E et al. (2010) Functional CCR5 receptor protects patients with arthritis from high synovial burden of infecting Chlamydia trachomatis. Am J Med Sci 340:448-51 |
| Gerard, Herve C; Whittum-Hudson, Judith A; Carter, John D et al. (2010) The pathogenic role of Chlamydia in spondyloarthritis. Curr Opin Rheumatol 22:363-7 |
| Gerard, Herve C; Stanich, Jessica A; Whittum-Hudson, Judith A et al. (2010) Patients with Chlamydia-associated arthritis have ocular (trachoma), not genital, serovars of C. trachomatis in synovial tissue. Microb Pathog 48:62-8 |
| Gerard, Herve C; Whittum-Hudson, Judith A; Carter, John D et al. (2009) Molecular biology of infectious agents in chronic arthritis. Rheum Dis Clin North Am 35:1-19 |
| Dreses-Werringloer, Ute; Bhuiyan, Mohammad; Zhao, Yinghao et al. (2009) Initial characterization of Chlamydophila (Chlamydia) pneumoniae cultured from the late-onset Alzheimer brain. Int J Med Microbiol 299:187-201 |
| Stanich, Jessica A; Carter, John D; Whittum-Hudson, Judith et al. (2009) Rheumatoid arthritis: Disease or syndrome? Open Access Rheumatol 1:179-192 |
| Wilson, David P; Whittum-Hudson, Judith A; Timms, Peter et al. (2009) Kinematics of intracellular chlamydiae provide evidence for contact-dependent development. J Bacteriol 191:5734-42 |
| Mayes, Maureen D; Whittum-Hudson, Judith A; Oszust, Cynthia et al. (2009) Lack of evidence for bacterial infections in skin in patients with systemic sclerosis. Am J Med Sci 337:233-5 |
| Balin, Brian J; Little, C Scott; Hammond, Christine J et al. (2008) Chlamydophila pneumoniae and the etiology of late-onset Alzheimer's disease. J Alzheimers Dis 13:371-80 |
| Jabs, Douglas A; Prendergast, Robert A; Campbell, Adam L et al. (2007) Autoimmune Th2-mediated dacryoadenitis in MRL/MpJ mice becomes Th1-mediated in IL-4 deficient MRL/MpJ mice. Invest Ophthalmol Vis Sci 48:5624-9 |
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