Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6125839 | Seminars in Immunology | 2016 | 15 Pages |
Abstract
Neutrophils play a critical role in the host defense against infection, and they are able to perform a variety of effector mechanisms for this purpose. However, there are also a number of pathological conditions, including autoimmunity and cancer, in which the activities of neutrophils can be harmful to the host. Thus the activities of neutrophils need to be tightly controlled. As in the case of other immune cells, many of the neutrophil effector functions are regulated by a series of immunoreceptors on the plasma membrane. Here, we review what is currently known about the functions of the various individual immunoreceptors and their signaling in neutrophils. While these immunoreceptors allow for the recognition of a diverse range of extracellular ligands, such as cell surface structures (like proteins, glycans and lipids) and extracellular matrix components, they commonly signal via conserved ITAM or ITIM motifs and their associated downstream pathways that depend on the phosphorylation of tyrosine residues in proteins and/or inositol lipids. This allows for a balanced homeostatic regulation of neutrophil effector functions. Given the number of available immunoreceptors and their fundamental importance for neutrophil behavior, it is perhaps not surprising that pathogens have evolved means to evade immune responses through some of these pathways. Inversely, some of these receptors evolved to specifically recognize these pathogens. Finally, some interactions mediated by immunoreceptors in neutrophils have been identified as promising targets for therapeutic intervention.
Keywords
IVIgGRB2PLCMLCKPKCGPiinositol triphosphateITIMDAP12GPCRPMNPIP3ADCCANCAsITAMGEFfMLPSH2IP3PI3KPI(3,4)P2GBSSLP-76MRP8SHPERKIgSFPtpn6ORFNADPHPIP2BtkMPOMAPKNETsPhosphatidylinositol-4,5-bisphosphate 3-kinaseROSRheumatoid arthritisantibody-dependent cellular cytotoxicityGroup B streptococciIntravenous immunoglobulinsneutrophil extracellular trapsBruton's tyrosine kinaseImmunoglobulin superfamilyPH domainPleckstrin homology domaindiacyl-glycerolDAGIRAKguanine nucleotide exchange factorphosphatidylethanolaminePhosphatidylserinephosphatidylinositol (3,4,5)-trisphosphatephosphatidylinositol (4,5)-bisphosphatephospholipase Copen reading frameSystemic lupus erythematosusSLEpolymorphonuclear leukocytesImmunoreceptor tyrosine-based inhibitory motifmyeloperoxidasenicotinamide adenine dinucleotide phosphateSrc Homology 2Protein kinase Cmitogen-activated protein kinasegrowth factor receptor-bound protein 2SHIPextracellular signal-regulated kinaseMyosin light-chain kinaseInterleukin-1 receptor-associated kinaseglycophosphatidylinositolReactive oxygen speciesG protein-coupled receptor
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Authors
Dieke J. van Rees, Katka Szilagyi, Taco W. Kuijpers, Hanke L. Matlung, Timo K. van den Berg,