Neutrophil signaling pathways activated by bacterial DNA stimulation.

ALVAREZ ME; BASS JI; JORGE GEFFNER; FERNÁNDEZ-CALOTTI, PAULA; MONICA ALEJANDRA COSTAS; COSO O.A.; ROMINA GAMBERALE; VERMEULEN ME; SALAMONE G; TREVANI AS

J Immunol

Año: 2006 vol. 177 p. 4037 - 4046

We have previously shown that bacterial DNA activates human neutrophils in a CpG-independent manner. In this study, we have characterized the signaling pathways involved in the activation mechanism. We found that p38 MAPK, ERK1/2, and JNK pathways, as well as the PI3K/Akt pathway, are activated by bacterial DNA. We also determined that bacterial DNA induces NF-
B and AP-1 activation. When analyzing the role of these pathways on neutrophil functions, we observed that up-regulation of CD11b triggered by bacterial DNA was decreased by pharmacological inhibitors of the p38 MAPK, ERK1/2, and JNK, whereas stimulation of IL-8 release was dependent on p38, ERK1/2, and NF-
B. Moreover, we found that IL-8 production was markedly enhanced by inhibition of JNK, suggesting that this pathway negatively modulates NF-
B-dependent transcription. We also observed that bacterial DNA stimulated IL-1R-associated kinase-1 kinase activity and its partial degradation. Finally, we determined that bacterial DNA stimulated CD11b up-regulation in TLR9/ but not in MyD88/ mouse neutrophils, supporting that bacterial DNA induces neutrophil activation through a TLR9-independent and MyD88-dependent pathway. The Journal of Immunology, 2006, 177: 4037–4046.