Broad-spectrum antibiotics affect CCR4+ and CCR6+ Th17 and Treg recruitment to the gingiva 2259700

Abstract

Abstract Introduction Susceptibility to periodontitis depends on the interplay between the oral plaque microbiota and host immune response. IL-17A-producing CD4 T cells (Th17) and regulatory T cells (Tregs) expressing either CCR4+ or CCR6+ are both present in human periodontitis. Oral vancomycin decreases intestinal priming of CCR6+ Th17, reducing their recruitment to the oral mucosa, which mitigates murine ligature-induced periodontitis (LIP). Yet, it is unclear how the oral microbiota affects the relative proportions of Th17 and Tregs. We hypothesized that broad-spectrum antibiotic treatment decreases the frequency of CCR4+ and CCR6+ Th17 cells to protect against LIP. Methods C57BL6 mice were pre-treated with (i) water alone or water containing (ii) broad-spectrum systemically absorbable antibiotics alternating weekly with non-absorbable antibiotics for 27 days. Periodontitis was induced with ligatures placed around upper molars concurrent with human oral pathobiont Porphyromonas gingivalis (Pg). In the gingival tissues, the frequencies of CCR4+, CCR6+, and CCR9+ CD4 T cells were assessed with flow cytometry, while CCL2, 17, 20, 22, or 25 mRNA expression was measured using qPCR. Results Broad-spectrum antibiotics reduced the frequency of both CCR4+ and CCR6+ Th17 and Tregs in the gingival tissues at 10 days after LIP induction. Broad-spectrum antibiotics reduced the frequency of CCR9+ Tregs at 10 days after LIP. CCR9+ Th17 cells were not detected. In the absence of antibiotic treatment, only CCL22 chemokine mRNA was elevated 10 days after LIP. Conclusion The protective effect of broad-spectrum antibiotics is associated with a reduction in CCR4+ and CCR6+ Th17 cells in the gingiva, despite a concurrent reduction in Tregs. A targeted reduction in Th17 cells may benefit human periodontitis irrespective of CCR4+ and CCR6+ Tregs. We speculate that broad-spectrum antibiotic treatment would reduce CCL22. Intestinal T cell priming drives CCR9+ Tregs but not Th17 cells to the gingiva. Funding Source NIH NIDCR NATL INST OF DENTAL 1R01DE030095-01A1 Topic Categories Cytokines and Chemokines and their Receptors (CCR)