Toll-like Receptors: Implication in Human Disease

Abstract

The innate immune system includes macrophages and natural killer (NK) cells, which may act directly on the pathogen or, by releasing cytokines and expressing other stimulatory molecules, trigger adaptative immune response by activating T and B cells. The strategy of the innate immune response may not be to recognize every single antigen, but rather to focus on few, highly conserved structures which are referred to as pathogen-associated molecular patterns (PAMPs). The receptors of the innate immune system that have evolved to recognize the PAMPs are called pattern-recognition receptors (Table 1). These activate signal-transduction pathways that induce the expression of a variety of immune-response genes, including inflammatory cytokines [1]. The recently identified receptors of the Toll family appear to have a major role in the induction of immune and inflammatory responses. Two discoveries support this role: the implication of the Toll-like receptors (TLRs) in innate immunity in Drosophila [2], and the identification of a TLR homolog as the gene responsible for lipopolysaccharide (LPS) responses in two natural mouse mutants [3,4].