The expression and roles of Toll-like receptors in the biology of the human neutrophil. Journal of leukocyte biology 77

Abstract: Neutrophils are amongst the first im-mune cells to arrive at sites of infection, where they initiate antimicrobial and proinflammatory func-tions, which serve to contain infection. Sensing and defeating microbial infections are daunting tasks as a result of their molecular heterogeneity; however, Toll-like receptors (TLRs) have emerged as key components of the innate-immune system, activat-ing multiple steps in the inflammatory reaction, eliminating invading pathogens, and coordinating systemic defenses. Activated neutrophils limit in-fection via the phagocytosis of pathogens and by releasing antimicrobial peptides and proinflamma-tory cytokines and generating reactive oxygen in-termediates. Through the production of chemo-kines, they additionally recruit and activate other immune cells to aid the clearance of the microbes and infected cells and ultimately, mount an adap-tive immune response. In acute inflammation, in-flux of neutrophils from the circulation leads to extremely high cell numbers within tissues, which is exacerbated by their delayed, constitutive apopto-sis caused by local inflammatory mediators, poten-tially including TLR agonists. Neutrophil apoptosis and safe removal by phagocytic cells limit tissue damage caused by release of neutrophil cytotoxic granule contents. This review addresses what is currently known about the function of TLRs in the biology of the human neutrophil, including the reg-ulation of TLR expression, their roles in cellular recruitment and activation, and their ability to de-lay apoptotic cell death. J. Leukoc. Biol. 77