Chronic 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 sevenfold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation after MI through memory T-cell activation. We compared four groups [no MI, chronic LPS, after MI, and after MI with chronic LPS (LPS + MI); = 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 ( < 0.05 vs. all). Memory CD8 T cells (CD44CD27) were 10-fold greater in LPS + MI than in MI alone ( = 0.02). Interleukin (IL)-4 stimulated splenic CD8 T cells away from an effector phenotype and toward 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 after 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 are amplified by chronic LPS to potentially promote infarct wall thinning. Although there is a well-documented link between periodontal disease and heart health, the mechanisms are unclear. Our study indicates that in response to circulating periodontal endotoxins, memory CD8 T cells are activated, resulting in an acceleration of macrophage-mediated inflammation after MI. Blocking activation of effector CD8 T cells had no effect on the macrophage numbers or wall thinning at post-MI , indicating that this response was likely due in part to memory CD8 T cells.