Background/Purpose: The obligate intracellular pathogen, Chlamydia, is the most common cause of reactive arthritis (ReA). We have demonstrated that susceptibility to experimental Chlamydia-induced ReA is determined as early as day 4 post infection implicating the innate immune response. However the cellular and molecular mechanisms during this stage have yet to be determined. Here we demonstrate the importance of the macrophage in directing both innate and adaptive immune responses to Chlamydia, and limiting dissemination of the organism.

Methods: Clodronate liposomes (CL) were used to deplete peritoneal macrophages with PBS-liposomes (PL) acting as the control. Clodronate did not affect neutrophil or lymphocyte populations. Subsequent to macrophage depletion mice were infected IP with 107 IFU Chlamydia muridarum for either 7 or 14 days. Spleens, peritoneal lavage, peritoneal membranes and blood were harvested for analysis of immune response and Chlamydia load.

Results: There was no mortality, nor signs of systemic disease associated with Chlamydia challenge in macrophage-depleted mice. Inspection of peritoneal cavity cells at day 7 demonstrated depletion of Cd11b+F4/80+ macrophages (PL; 50% of cells, CL; 5% of cells) and a significant increase in CD11b+Ly6G+ neutrophils (PL; 10% of cells, CL; 60% of cells) was seen in the mice treated with clodronate liposomes. This was coupled with a 5-fold increase in Chlamydia 16sRNA load of these cells as assessed by qPCR. 16sRNA was only detected in blood samples only in the macrophage-depleted mice, reflecting dissemination of the organism beyond the site of local challenge. At day 14 post Chlamydia infection, depletion of macrophages was associated with a significant alteration of the adaptive immune response profile, with reduced numbers of Th1 cells and activated IFNy+, CD8+ cells. This was coupled with a 20-fold increase chlamydial load compared to control mice

Conclusion: These data indicate that macrophages are crucial in defining effective host innate immune response to Chlamydia and thereby limiting dissemination of the organism. In addition, macrophages orchestrate the development of effective adaptive host response to the organism. These studies suggest that quantitative or qualitative alteration in macrophages may play a key role in the development of post-Chlamydia sequelae such as reactive arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/with-chlamydia-infection-the-macrophage-serves-as-gate-keeper-for-dissemination-and-induction-of-host-immunity/