Trends in Immunology
ReviewPattern recognition receptor function in neutrophils
Section snippets
The multifarious functions of neutrophils and PRRs
The innate immune system uses a broad array of PRRs to detect invariant structural motifs on invading pathogens (pathogen-associated molecular patterns, PAMPs) and endogenous danger signals indicating host injury or stress (danger-associated molecular patterns, DAMPs) [1]. Such receptors include membrane-bound receptors that scan the extracellular milieu and endosomal compartments (e.g., Toll-like receptors, TLRs; and C-type lectin receptors, CLRs), cytoplasmic nucleic acid-sensing receptors
Neutrophil TLRs
TLRs are expressed on the cell surface and on endolysosomal membranes, and primarily recognize PAMPs derived from bacteria, fungi, and viruses (Figure 1). TLR ligation has been predominantly studied in macrophages, where signaling generally culminates in the activation of a range of transcription factors [e.g., nuclear factor (NF)-κB, activator protein (AP)-1 and interferon (IFN) regulatory factor (IRF) family members] and triggers the production of proinflammatory cytokines and type I IFNs (
Neutrophil CLRs
CLRs are a diverse family of proteins that possess one or more C-type lectin-like domains that recognize carbohydrate moieties. Although many CLRs are not PRRs, those that do act as PRRs have critical roles in innate immunity, particularly against fungi. Most PRRs of the CLR family either bear an intracellular immunoreceptor tyrosine-based activation-like motif (ITAM) or associate with ITAM-containing adaptor proteins. Ligand binding of these CLRs triggers phosphorylation of ITAMs and
Neutrophil NLRs
NLRs are a family of cytoplasmic PRRs (Figure 1). The molecular functions of most NLRs, including those expressed in neutrophils (Table 3), remain poorly described. However, the function of characterized NLRs cluster with phylogenetic relations [42]; NODs 1 and 2 regulate NF-κB and MAPK activity, whereas NLRP3, NLRP1, and NLRC4 form inflammasomes (Figure 2).
Other neutrophil PRRs
Other PRR receptor family members with established or emerging roles in regulating neutrophil function during infection include FPRs, RIG-like helicases (RLHs), hematopoietic IFN-inducible nuclear antigens with 200 amino acid repeats (HIN-200) proteins, and triggering receptors expressed on myeloid cells (TREMs) (Table 4). FPRs, such as FPR1 and FPR2 that recognize bacterial and mitochondrial f-Met-Leu-Phe, are G-coupled protein receptors that trigger murine and human neutrophil degranulation,
Concluding remarks
Neutrophils are multifunctional cells that orchestrate a complex series of events during infection and inflammation. They rapidly accrue at a site of insult through their abilities to migrate quickly into tissues and delay their preprogrammed death. Upon encountering microbes, they unleash their considerable antimicrobial arsenal (e.g., ROS, granule proteins, NETs; Box 1, Box 2), program the future immune response through secretion of pro- and anti-inflammatory cytokines (Box 3), and limit
Acknowledgments
C.J.T. is supported by postgraduate scholarships from the Natural Science and Engineering Research Council of Canada, and is a member of the TUM Graduate School. K.S. is supported by the National Health and Medical Research Council of Australia (C.J. Martin Fellowship and Project Grant, IDs 490993 and 1023297) and the Queensland Smart Futures Fund.
References (95)
- et al.
Pattern recognition receptors and inflammation
Cell
(2010) - et al.
Neutrophil clearance: when the party is over, clean-up begins
Trends Immunol.
(2011) Toll-like receptors stimulate human neutrophil function
Blood
(2003)Selective and direct activation of human neutrophils but not eosinophils by Toll-like receptor 8
J. Allergy Clin. Immunol.
(2009)Toll-like receptor-mediated activation of neutrophils by influenza A virus
Blood
(2008)The role of TLRs in neutrophil activation
Curr. Opin. Pharmacol.
(2011)The beta-glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance
Cell Host Microbe
(2011)Complement receptor 3, not Dectin-1, is the major receptor on human neutrophils for beta-glucan-bearing particles
Mol. Immunol.
(2009)Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils
Immunity
(2009)Neutrophil-derived proteins: selling cytokines by the pound
Adv. Immunol.
(1999)