High Chlamydia Burden Promotes Tumor Necrosis Factor-Dependent Reactive Arthritis in SKG Mice.

Baillet, AC; Rehaume, LM; Benham, H; O'Meara, CP; Armitage, CW; Ruscher, R; Brizard, G; Harvie, MCG; Velasco, J; Hansbro, PM; Forrester, JV; Degli-Esposti, MA; Beagley, KW; Thomas, R

High Chlamydia Burden Promotes Tumor Necrosis Factor-Dependent Reactive Arthritis in SKG Mice.

Baillet, AC Rehaume, LM Benham, H O'Meara, CP Armitage, CW Ruscher, R Brizard, G Harvie, MCG Velasco, J Hansbro, PM Forrester, JV Degli-Esposti, MA Beagley, KW Thomas, R

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Publisher:: WILEY-BLACKWELL
Publication Type:: Journal Article
Citation:: Arthritis & rheumatology (Hoboken, N.J.), 2015, 67, (6), pp. 1535-1547
Issue Date:: 2015-06

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Field	Value	Language
dc.contributor.author	Baillet, AC
dc.contributor.author	Rehaume, LM
dc.contributor.author	Benham, H
dc.contributor.author	O'Meara, CP
dc.contributor.author	Armitage, CW
dc.contributor.author	Ruscher, R
dc.contributor.author	Brizard, G
dc.contributor.author	Harvie, MCG
dc.contributor.author	Velasco, J
dc.contributor.author	Hansbro, PM
dc.contributor.author	Forrester, JV
dc.contributor.author	Degli-Esposti, MA
dc.contributor.author	Beagley, KW
dc.contributor.author	Thomas, R
dc.date.accessioned	2021-03-03T05:33:12Z
dc.date.available	2015-01-15
dc.date.available	2021-03-03T05:33:12Z
dc.date.issued	2015-06
dc.identifier.citation	Arthritis & rheumatology (Hoboken, N.J.), 2015, 67, (6), pp. 1535-1547
dc.identifier.issn	2326-5191
dc.identifier.issn	2326-5205
dc.identifier.uri	http://hdl.handle.net/10453/146720
dc.description.abstract	<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
dc.format	Print
dc.language	eng
dc.publisher	WILEY-BLACKWELL
dc.relation.ispartof	Arthritis & rheumatology (Hoboken, N.J.)
dc.relation.isbasedon	10.1002/art.39041
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences, 1107 Immunology, 1117 Public Health and Health Services
dc.subject.classification	Arthritis & Rheumatology
dc.subject.mesh	T-Lymphocytes
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred Strains
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Mice
dc.subject.mesh	Chlamydia muridarum
dc.subject.mesh	Chlamydia Infections
dc.subject.mesh	Vaginosis, Bacterial
dc.subject.mesh	Arthritis, Reactive
dc.subject.mesh	Respiratory Tract Infections
dc.subject.mesh	Inflammatory Bowel Diseases
dc.subject.mesh	Psoriasis
dc.subject.mesh	Tumor Necrosis Factor-alpha
dc.subject.mesh	Interleukin-17
dc.subject.mesh	Antibodies, Bacterial
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	T-Lymphocytes, Regulatory
dc.subject.mesh	Interferon-gamma
dc.subject.mesh	Reproductive Tract Infections
dc.subject.mesh	Animals
dc.subject.mesh	Antibodies, Bacterial
dc.subject.mesh	Arthritis, Reactive
dc.subject.mesh	Chlamydia Infections
dc.subject.mesh	Chlamydia muridarum
dc.subject.mesh	Female
dc.subject.mesh	Inflammatory Bowel Diseases
dc.subject.mesh	Interferon-gamma
dc.subject.mesh	Interleukin-17
dc.subject.mesh	Male
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Mice, Inbred Strains
dc.subject.mesh	Psoriasis
dc.subject.mesh	Reproductive Tract Infections
dc.subject.mesh	Respiratory Tract Infections
dc.subject.mesh	T-Lymphocytes
dc.subject.mesh	T-Lymphocytes, Regulatory
dc.subject.mesh	Tumor Necrosis Factor-alpha
dc.subject.mesh	Vaginosis, Bacterial
dc.title	High Chlamydia Burden Promotes Tumor Necrosis Factor-Dependent Reactive Arthritis in SKG Mice.
dc.type	Journal Article
utslib.citation.volume	67
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1107 Immunology
utslib.for	1117 Public Health and Health Services
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
dc.date.updated	2021-03-03T05:33:10Z
pubs.issue	6
pubs.publication-status	Published
pubs.volume	67
utslib.citation.issue	6

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/146720