Zhang Xiaoming, Majlessi Laleh, Deriaud Edith, Leclerc Claude, Lo-Man Richard
Institut Pasteur, Unité Régulation Immunitaire et Vaccinologie, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Immunity. 2009 Nov 20;31(5):761-71. doi: 10.1016/j.immuni.2009.09.016. Epub 2009 Nov 12.
Neutrophils are one of the first lines of defense against microbial pathogens and are rapidly recruited at the infection site upon inflammatory conditions. We show here that after bacterial stimulation, and in contrast to monocytes and macrophages, murine neutrophils contributed poorly to inflammatory responses; however, they secreted high amounts of the anti-inflammatory cytokine IL-10 in a DAP12 adaptor-Syk kinase and MyD88 adaptor-dependent manner. Cotriggering of TLR-MyD88- and C-type lectin receptor (CLR)-Syk-dependent pathways led to a quick and sustained phosphorylation of p38 MAP and Akt kinases in neutrophils. In vivo, both Gram-negative bacteria and mycobacteria induced the recruitment of neutrophils secreting IL-10. In acute mycobacterial infection, neutrophil-derived IL-10 controlled the inflammatory response of dendritic cells, monocytes and macrophages in the lung. During a chronic infection, neutrophil depletion promoted inflammation and decreased the mycobacterial burden. Therefore, neutrophils can have a previously unsuspected regulatory role during acute and chronic microbial infections.
中性粒细胞是抵御微生物病原体的第一道防线之一，在炎症条件下会迅速募集到感染部位。我们在此表明，与单核细胞和巨噬细胞不同，细菌刺激后，小鼠中性粒细胞对炎症反应的贡献较小；然而，它们以依赖DAP12衔接蛋白-Syk激酶和MyD88衔接蛋白的方式分泌大量抗炎细胞因子IL-10。TLR-MyD88依赖性途径和C型凝集素受体（CLR）-Syk依赖性途径的共同触发导致中性粒细胞中p38 MAP和Akt激酶快速且持续的磷酸化。在体内，革兰氏阴性菌和分枝杆菌均可诱导分泌IL-10的中性粒细胞的募集。在急性分枝杆菌感染中，中性粒细胞衍生的IL-10控制了肺中树突状细胞、单核细胞和巨噬细胞的炎症反应。在慢性感染期间，中性粒细胞耗竭会促进炎症并降低分枝杆菌负荷。因此，中性粒细胞在急性和慢性微生物感染期间可能具有此前未被怀疑的调节作用。
