Immune response to Porphyromonas gingivalis antigens exacerbates hypertension

Periodontal disease has been recently established as a pathogenetic factor for vascular dysfunction and atherosclerosis. Its relationship to hypertension, the most prevalent cardiovascular disease, remains unknown. Objective: As T cell activation has recently been described as an important regulator of blood pressure, we postulated that the oral pathogen Porphyromonas gingivalis (Pg.) could induce T cell activation, leading subsequently to hypertension. Methods: Pg. antigens isolated from bacteria were conjugated with Alum/IL-12 (inducing T helper Th1 response with IFN-g and TNF release) or without IL-12 (Th2 response with IL-5, IL-4) and injected i.p. in C57Bl6/J mice twice 3 weeks apart. 5 days after the 2nd Pg immunization low dose angiotensin II (0.35mg/day/kg) was infused for 14 days via osmotic minipump. Blood pressure was measured by tail cuff; T cell properties were studied by flow cytometry and vascular function was assessed. Results: Induction of T cell responses to Pg. antigens significantly increased hypertensive response to angiotensin II in mice (155±3 vs. 134±2mmHg in controls; p<0.001). Blood pressures are higher when Th2 immune response is induced (160±3 vs 146±3 mmHg in Th1; p=0.05). This increase of blood pressure in Pg stimulated mice was accompanied by development of vascular dysfunction and oxidative stress. Both Th1 and Th2 type response was associated with increased peripheral T cell activation (CD69 13.5±2% in Th1 vs. 12.9±1% in Th2 vs 8±1% in controls), CD11b(ICAM1receptor) and CCR5 chemokine receptor expression allowing for their vascular infiltration. Induction of Pg specific T cells increased infiltration of T cells into the aorta (7.7e4±2e4 CD3+ cells in control vs 13.9e4±4e4 cells/aorta in Th1 vs 27e4±6e4 cells /aorta in Th2 induced mice; p<0.001). Conclusions: T cell immune responses against Porphyromonas gingivalis antigens lead to increased angiotensin II induced hypertension through T cell activation and their vascular infiltration leading to vascular dysfunction.