Editors' ChoiceImmunology

Regulatory Neutrophils

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Science Signaling  24 Nov 2009:
Vol. 2, Issue 98, pp. ec376
DOI: 10.1126/scisignal.298ec376

Neutrophils are among the first responders at sites of infection and are an essential arm of the innate immune system. They attack invading pathogens through a number of mechanisms, including phagocytosis and the release of lytic enzymes and reactive oxygen species, leading to an acute proinflammatory response (see commentary by Cassatella et al.). Zhang et al. investigated the responses of mouse neutrophils to bacteria and various agonists of pattern-recognition receptors, such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs). Whereas individual TLR agonists (particularly Pam3, which stimulates TLR2) activated neutrophils in vitro, they did not induce the production of proinflammatory cytokines; rather, they stimulated neutrophils to produce small quantities of the anti-inflammatory cytokine interleukin-10 (IL-10). Exposure of neutrophils to bacteria resulted in the production of much greater amounts of IL-10, which led the authors to investigate which other signals might synergize with TLR agonists in IL-10 production. Coactivation of TLR2 and the CLR Dectin-1, which recognizes carbohydrate moieties on bacteria and fungi, stimulated neutrophils to produce large quantities of IL-10, an effect that depended on MyD88 (an adaptor protein that is part of the TLR2 pathway) and the tyrosine kinase Syk, which mediates CLR-dependent responses. Synergy between the CLR and TLR2 pathways depended on the activation of p38 mitogen-activated protein kinase and Akt. Neutrophils isolated from the lungs of mice 5 weeks after infection with Mycobacterium tuberculosis produced large amounts of IL-10. When neutrophils were depleted from these mice, proinflammatory dendritic cells and cytokines became more abundant in the lung and the number of bacteria was substantially reduced. Together, these data suggest that neutrophils can respond to pathogens by producing IL-10 to modulate the inflammatory response.

X. Zhang, L. Majlessi, E. Deriaud, C. Leclerc, R. Lo-Man, Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity 31, 761–771 (2009). [PubMed]

M. A. Cassatella, M. Locati, A. Mantovani, Never underestimate the power of a neutrophil. Immunity 31, 698–700 (2009). [Online Journal]

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