The recognition of microbial structures by Toll-like receptors (TLRs) on professional immune cells situated at sterile internal body sites occurs during invasive microbial infection. It indicates infectious non-self and thereby represents the adequate co-stimulatory signal to initiate activation of the adaptive immune system against the invading pathogen. In contrast, most epithelial body surfaces are permanently colonized by microbial organisms of the normal flora and thus TLR ligands are present under physiological conditions. In the following, we discuss the characteristics of TLR-mediated recognition by epithelial cells, the subsequent activation of the host immune system, and protective mechanisms that might help to avoid inadequate stimulation and allow differentiation between commensal or pathogenic micro-organisms. Recent findings suggest that the role of epithelial cells in the maintenance of stable microbial colonization of host surfaces and the immediate host response to infectious challenges might have to be revised.
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