Chronic Porphyromonas gingivalis lipopolysaccharide induces adverse myocardial infarction wound healing through activation of CD8+ T-cells.

Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by seven-fold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation post-MI through memory T-cell activation. We compared 4 groups (no MI, chronic LPS, day 1 post-MI, and day 1 post-MI with chronic LPS (LPS+MI); n=68 mice) using the mouse heart attack research tool 1.0 database and tissue bank coupled with new analyses and experiments. LPS+MI increased total CD8+ T-cells in the left ventricle versus the other groups (p<0.05 versus all). Memory CD8+ T-cells (CD44+CD27+) were 10-fold greater in LPS+MI compared to MI alone (p=0.02). Interleukin (IL)-4 stimulated splenic CD8+ T-cells away from an effector phenotype and towards a memory phenotype, inducing secretion of factors associated with the Wnt/β-catenin signaling that promoted monocyte migration and decreased viability. To dissect the effect of CD8+ T-cells post-MI, we administered a major histocompatibility complex-I blocking antibody starting 7 days before MI, which prevented effector CD8+ T-cell activation without affecting the memory response. The reduction in effector cells diminished infarct wall thinning but had no effect on macrophage numbers or MertK expression. LPS+MI+IgG attenuated macrophages within the infarct without effecting CD8+ T-cells suggesting these two processes were independent. Overall, our data indicate that effector and memory CD8+ T-cells at post-MI day 1 are amplified by chronic LPS to potentially promote infarct wall thinning.