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Since intracellular pathogens enhance their replicative fitness in stressed host cells, we examined how myeloid cells infected with <jats:italic>C muridarum<\/jats:italic> drive arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SKG, <jats:italic>Il17a<\/jats:italic>\u2010deficient SKG, and BALB\/c female mice were infected with <jats:italic>C muridarum<\/jats:italic> or <jats:italic>C muridarum<\/jats:italic> luciferase in the genitals. <jats:italic>C muridarum<\/jats:italic> dissemination was assessed by in vivo imaging or genomic DNA amplification. Macrophages were depleted using clodronate liposomes. Anti\u2013tumor necrosis factor (anti\u2010TNF) and anti\u2013interleukin\u201023p19 (anti\u2013IL\u201023p19) were administered after infection or arthritis onset. Gene expression of <jats:italic>Hspa5<\/jats:italic>, <jats:italic>Tgtp1<\/jats:italic>, <jats:italic>Il23a<\/jats:italic>, <jats:italic>Il17a<\/jats:italic>, <jats:italic>Il12b<\/jats:italic>, and <jats:italic>Tnf<\/jats:italic> was compared in SKG mice and BALB\/c mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One week following infection with <jats:italic>C muridarum<\/jats:italic>, macrophages and neutrophils were observed to have infiltrated the uteri of mice and were also shown to have carried <jats:italic>C muridarum<\/jats:italic> DNA to the spleen. <jats:italic>C muridarum<\/jats:italic> load was higher in SKG mice than in BALB\/c mice. Macrophage depletion was shown to reduce <jats:italic>C muridarum<\/jats:italic> load and prevent development of arthritis. Compared with BALB\/c mice, expression of <jats:italic>Il23a<\/jats:italic> and <jats:italic>Il17a<\/jats:italic> was increased in the uterine and splenic neutrophils of SKG mice. The presence of anti\u2013IL\u201023p19 during infection or <jats:italic>Il17a<\/jats:italic> deficiency suppressed arthritis. <jats:italic>Tnf<\/jats:italic> 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\u2010related GTPase, by <jats:italic>C muridarum<\/jats:italic> infection in the uterus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>C muridarum<\/jats:italic> load is higher in SKG mice than in BALB\/c mice. Whereas proinflammatory IL\u201023 produced by neutrophils contributes to the initiation of <jats:italic>C muridarum<\/jats:italic>\u2013mediated ReA, macrophage depletion reduces <jats:italic>C muridarum<\/jats:italic> 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41653","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T06:07:50Z","timestamp":1610777270000},"page":"1200-1210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mediation of Interleukin\u201023 and Tumor Necrosis Factor\u2013Driven Reactive Arthritis by <i>Chlamydia<\/i>\u2010Infected Macrophages in SKG Mice"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2222-1456","authenticated-orcid":false,"given":"Xavier","family":"Romand","sequence":"first","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes GREPI TIMC\u2010IMAG UMR 5525  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Queensland Diamantina Institute and Princess Alexandra Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arifur","family":"Rahman","sequence":"additional","affiliation":[{"name":"University of Queensland Diamantina Institute and Princess Alexandra Hospital  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaied Ahmed","family":"Bhuyan","sequence":"additional","affiliation":[{"name":"University of Queensland Diamantina Institute and Princess Alexandra Hospital, Brisbane, Queensland, Australia, and North South University  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Douillard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes GREPI TIMC\u2010IMAG UMR 5525  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena Arora","family":"Kedia","sequence":"additional","affiliation":[{"name":"University of Queensland Diamantina Institute and Princess Alexandra Hospital  Brisbane Queensland 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