High Chlamydia burden promotes TNF-dependent reactive arthritis in SKG mice

Baillet, Athan C., Rehaume, Linda, Benham, Helen, O'Meara, Connor P., Armitage, Charles W., Ruscher, Roland, Brizard, Geraldine, Harvie, Marina C. G., Velasco, Jared, Hansbro, Phillip, Forrester, John V., Degli-Esposti, Mariapia, Beagley, Kenneth W. and Thomas, Ranjeny (2015) High Chlamydia burden promotes TNF-dependent reactive arthritis in SKG mice. Arthritis and Rheumatology, 67 6: 1535-1547. doi:10.1002/art.39041

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ353054_OA.pdf Full text (open access) application/pdf 1.75MB 0

Author Baillet, Athan C.
Rehaume, Linda
Benham, Helen
O'Meara, Connor P.
Armitage, Charles W.
Ruscher, Roland
Brizard, Geraldine
Harvie, Marina C. G.
Velasco, Jared
Hansbro, Phillip
Forrester, John V.
Degli-Esposti, Mariapia
Beagley, Kenneth W.
Thomas, Ranjeny
Title High Chlamydia burden promotes TNF-dependent reactive arthritis in SKG mice
Journal name Arthritis and Rheumatology   Check publisher's open access policy
ISSN 2326-5191
2326-5205
Publication date 2015-06-01
Year available 2015
Sub-type Article (original research)
DOI 10.1002/art.39041
Volume 67
Issue 6
Start page 1535
End page 1547
Total pages 13
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2016
Language eng
Formatted abstract
Objective: Chlamydia trachomatis is a sexually-transmitted obligate intracellular pathogen, which causes inflammatory “reactive” arthritis, spondylitis, psoriasiform dermatitis and conjunctivitis in some individuals after genital infection. The immunological basis for this inflammatory response in susceptible hosts is poorly understood. As BALB/c ZAP70W163C-mutant (SKG) mice are susceptible to spondyloarthropathy after systemic exposure to microbial β-glucan, we compared the response of SKG and BALB/c mice to C. muridarum infection.

Methods: After genital or respiratory infection with C. muridarum, conjunctivis and arthritis were assessed clinically. Eye, skin and joint histological sections were scored. Chlamydial MOMP antigen-specific responses were assessed in splenocytes. Regulatory T cells were depleted from FoxP3-DTR BALB/c or SKG mice. Chlamydial DNA was quantified by PCR.

Results: Female SKG but not BALB/c mice developed arthritis, spondylitis and psoriasiform dermatitis, but not inflammatory bowel disease, 5 weeks after vaginal infection with live C. muridarum. Inflammatory disease severity was correlated with C. muridarum inoculum size and vaginal burden post-inoculation. Combination antibiotics 1 day post-inoculation prevented disease. Chlamydial antigen was present in macrophages and spread from infection site to lymphoid organs and peripheral tissues. In response to Chlamydial antigen, SKG T cells made impaired IFN-γ and IL-17, but exaggerated TNF responses compared to BALB/c T cells. Unlike arthritis triggered by β-glucan, no autoantibodies developed. Accelerated disease triggered by depletion of regulatory T 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. 
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Accepted manuscript published online ahead of print January 15, 2015.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 8 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 05 Mar 2015, 23:00:04 EST by Kylie Hengst on behalf of UQ Diamantina Institute