GM-CSF enhances a CpG-independent pathway of neutrophil activation triggered by bacterial DNA.
We have previously demonstrated that bacterial DNA induces neutrophil activation through a CpG- and TLR9-independent but MyD88-dependent-pathway. In this study we determined that GM-CSF enhances the activation of neutrophils by bacterial DNA. Granulocyte-macrophage colony-stimulating factor increased IL-8 and IL-1beta secretion, and CD11b-upregulation induced by single-stranded bacterial DNA. It also enhanced neutrophil IL-8 production induced by double-stranded bacterial DNA, methylated single-stranded DNA, plasmid DNA, and phosphorothioated-CpG and non-CpG-oligodeoxynucleotides. Together these observations indicated that GM-CSF enhances neutrophil responses triggered by bacterial DNA in a CpG-independent fashion. We also found that GM-CSF enhanced the activation of the MAPKs p38 and ERK1/2 induced by bacterial DNA. Moreover, the pharmacological inhibition of these pathways significantly diminished GM-CSF ability to increase neutrophil activation by bacterial DNA. Finally, we observed that GM-CSF was unable to increase the activation of MyD88(-/-) neutrophils by bacterial DNA. Our findings suggest that GM-CSF modulates the CpG-independent, MyD88-dependent neutrophil response to bacterial DNA, by increasing the activation of the MAPKs p38 and ERK1/2.
Fuxman Bass
Juan I
JI
Departamento de Inmunología, Instituto de Investigaciones Hematológicas e Instituto de Estudios Oncológicos "Fundación Maissa"; Academia Nacional de Medicina, Buenos Aires, Argentina.
Alvarez
María E
ME
Gabelloni
María L
ML
Vermeulen
Mónica E
ME
Amaral
María M
MM
Geffner
Jorge R
JR
Trevani
Analía S
AS
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics*; D004269:DNA, Bacterial / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D039481:CD11b Antigen; D004269:DNA, Bacterial; D016209:Interleukin-8; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases