Pathogen Induced Chronic Inflammatory Disorders
Chronic inflammation culminates in devastating events, results in significant host pathology, and is associated with a number of human diseases including autoimmune diseases, infectious diseases, neoplastic diseases, and inflammatory atherosclerosis. Our studies focus on two pathogens associated with chronic inflammation, Chlamydia pneumoniae and Porphyromonas gingivalis. C. pneumoniae is a respiratory pathogen that causes a mild, usually asymptomatic pneumonia. P. gingivalis induces a local host inflammatory response that results in inflammatory bone destruction, which is manifested as periodontal disease. Normally, the acute inflammatory response is self-limited, working to contain these infections until the adaptive immune response is activated. However, under some circumstances, a chronic inflammatory state can ensue, resulting in additional host pathology. Recently, both C. pneumoniae and P. gingivalis have been implicated in the pathogenesis of chronic inflammatory plaque formation although how these pathogens induce and maintain chronic inflammation is not well defined. Our laboratory has defined the role of specific innate immune signaling pathways in immune cells that contribute collectively to pathogen-induced chronic inflammation. We are examining in vitro model systems for platelets, endothelial cells, and macrophages. Using defined animal models of inflammation we are characterizing the roles of innate immune pathways in inflammatory processes in vivo. Enhanced understanding of the roles of specific innate immune signaling pathways, which participate in proinflammatory mediator expression and functional immune responses will provide a promising avenue for novel therapies for chronic inflammatory disorders.
Figure right: plaque accumulation in aortic arch of P.gingivalis-induced ApoE-/- mice
Figure left: P.gingivalis-conjugated CFSA infection of HAEC cells