Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils.
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.
Zhang
Xiaoming
X
Institut Pasteur, Unité Régulation Immunitaire et Vaccinologie, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Majlessi
Laleh
L
Deriaud
Edith
E
Leclerc
Claude
C
Lo-Man
Richard
R
D000818:Animals; D016753:Interleukin-10 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology
D047908:Intracellular Signaling Peptides and Proteins; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse