Role of TLR polymorphisms in immunosenescence

Abstract

Innate immunity provides a first line of host defense against infection through microbial recognition and killing while simultaneously activating a clonotypic immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition and function mainly by detection of pathogen-associated molecular patterns (PAMPs) that do not exist in the host. The different members of TLRs recognize several PAMPs, such as peptidoglycan for TLR2, lipopolysaccharide (LPS) for TLR4, flagellin for TLR5, and CpGDNA-repeats for TLR9. Several endogenous ligands of various TLRs have been also identified in the host. In this chapter, we describe the involvement of TLR-4 polymorphisms in immunosenescence, and in particular in age-related diseases, suggesting the crucial role of molecules of innate immunity on these diseases pathophysiology. Hence, we observed that proinflammatory alleles may be related to unsuccessful aging as atherosclerosis and Alzheimer's disease; reciprocally, controlling inflammatory status by antiinflammatory alleles may allow to better attain successful aging.