INNATE IMMUNITY AND HEART DISEASE


Anne A. Knowlton, M.D., University of California, Davis, CA, USA

The innate immune system is a primitive, rapid immune response that responds to detected threats by producing a rapid inflammatory response. A series of pattern recognition receptors (PRR) recognizes molecular patterns (pathogen associated molecular patterns or PAMPs) that are common to microbes and to danger signals (damage-associated molecular patterns or DAMPs) from injured cells. These signals can activate specific toll-like receptors (TLRs), which then activate a rapid inflammatory response. Innate immunity is essential, as adaptive immunity, which produces antibodies, takes 4-5 days for a complete response. The heart contains TLRs, of which TLR2 and 4 have been most studied. TLR2 and 4 can be activated by proteins and other molecules released by injured or stressed cardiac myocytes. In the failing rat heart heat shock protein (HSP) 60 is present on the surface of cardiac myocytes. We have previously shown that heat shock HSP60 activates TLR4 leading to NFkB activation and the production of inflammatory cytokines, which in turn causes apoptosis in other cardiac myocytes. Ischemia/reperfusion releases a host of molecules, which can lead to local activation of innate immunity, compounding injury. Thus, innate immunity is an important factor in the heart disease and the progression of heart failure.