Mediation of Interleukin-23 and Tumor Necrosis Factor-Driven Reactive Arthritis by Chlamydia-Infected Macrophages in SKG Mice
| Autor: | Timothy J. Wells, Amy J Cameron, Xiao Liu, Kenneth W. Beagley, Aurelie Bozon, Charles W. Armitage, Bertrand Favier, Claire Douillard, Zaied Ahmed Bhuyan, Zi Huai Chew, Linda M. Rehaume, Nathan Stone, Athan Baillet, Ranjeny Thomas, M. Arifur Rahman, Mohammed Habib, Reena Arora Kedia, Minh Vu Chuong Nguyen, Max Maurin, Dominique Roest, Philippe Gaudin, Xavier Romand |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Chlamydia muridarum Immunology Arthritis Spleen Arthritis Reactive Interleukin-23 Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine Rheumatology Interleukin 23 medicine Immunology and Allergy Animals Reactive arthritis Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins Monomeric GTP-Binding Proteins Mice Inbred BALB C ZAP-70 Protein-Tyrosine Kinase biology business.industry Interleukin-12 Subunit p40 Tumor Necrosis Factor-alpha Gene Expression Profiling Macrophages Interleukin-17 Chlamydia Infections medicine.disease biology.organism_classification Arthritis Experimental 030104 developmental biology medicine.anatomical_structure Interleukin-23 Subunit p19 Tumor necrosis factor alpha Female IL17A business 030215 immunology |
| Zdroj: | Arthritisrheumatology (Hoboken, N.J.)References. 73(7) |
| ISSN: | 2326-5205 |
| Popis: | ZAP-70SKG, Il17a-deficient SKG, and BALB/c female mice were infected with C muridarum or C muridarum luciferase in the genitals. C muridarum dissemination was assessed by in vivo imaging or genomic DNA amplification. Macrophages were depleted using clodronate liposomes. Anti-tumor necrosis factor (anti-TNF) and anti-interleukin-23p19 (anti-IL-23p19) were administered after infection or arthritis onset. Gene expression of Hspa5, Tgtp1, Il23a, Il17a, Il12b, and Tnf was compared in SKG mice and BALB/c mice.One week following infection with C muridarum, macrophages and neutrophils were observed to have infiltrated the uteri of mice and were also shown to have carried C muridarum DNA to the spleen. C muridarum load was higher in SKG mice than in BALB/c mice. Macrophage depletion was shown to reduce C muridarum load and prevent development of arthritis. Compared with BALB/c mice, expression of Il23a and Il17a was increased in the uterine and splenic neutrophils of SKG mice. The presence of anti-IL-23p19 during infection or Il17a deficiency suppressed arthritis. Tnf was overexpressed in the joints of SKG mice within 1 week postinfection, and persisted beyond the first week. TNF inhibition during infection or at arthritis onset suppressed the development of arthritis. Levels of endoplasmic reticulum stress were constitutively increased in the joints of SKG mice but were induced, in conjunction with immunity-related GTPase, by C muridarum infection in the uterus.C muridarum load is higher in SKG mice than in BALB/c mice. Whereas proinflammatory IL-23 produced by neutrophils contributes to the initiation of C muridarum-mediated ReA, macrophage depletion reduces C muridarum dissemination to other tissues, tissue burden, and the development of arthritis. TNF inhibition was also shown to suppress arthritis development. Our data suggest that enhanced bacterial dissemination in macrophages of SKG mice drives the TNF production needed for persistent arthritis. |
| Databáze: | OpenAIRE |
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