title: The expression and roles of Toll-like receptors in the biology of the human neutrophil.
abstract: Neutrophils are amongst the first immune cells to arrive at sites of infection, where they initiate antimicrobial and proinflammatory functions, 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, activating multiple steps in the inflammatory reaction, eliminating invading pathogens, and coordinating systemic defenses. Activated neutrophils limit infection via the phagocytosis of pathogens and by releasing antimicrobial peptides and proinflammatory cytokines and generating reactive oxygen intermediates. Through the production of chemokines, they additionally recruit and activate other immune cells to aid the clearance of the microbes and infected cells and ultimately, mount an adaptive immune response. In acute inflammation, influx of neutrophils from the circulation leads to extremely high cell numbers within tissues, which is exacerbated by their delayed, constitutive apoptosis caused by local inflammatory mediators, potentially 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 regulation of TLR expression, their roles in cellular recruitment and activation, and their ability to delay apoptotic cell death.
authors.affiliation: Academic Units of Respiratory, Medicine and Cell Biology, Section of Functional Genomics, Division of Genomic Medicine, University of Sheffield, UK. l.c.parker@sheffield.ac.uk
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Parker
authors.forename: Moira K B
authors.initials: MK
authors.lastname: Whyte
authors.forename: Steven K
authors.initials: SK
authors.lastname: Dower
authors.forename: Ian
authors.initials: I
authors.lastname: Sabroe
mesh_terms: D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D051193:Toll-Like Receptors
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors