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J Immunol. 2017 Apr 1;198(7):2865-2875. doi: 10.4049/jimmunol.1601465. Epub 2017 Feb 20.

Local TNFR1 Signaling Licenses Murine Neutrophils for Increased TLR-Dependent Cytokine and Eicosanoid Production.

Author information

1
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720; and.
2
Vision Science Program, School of Optometry, University of California Berkeley, Berkeley, CA 94598.
3
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720; and barton@berkeley.edu.

Abstract

Neutrophils are generally the first immune cells recruited during the development of sterile or microbial inflammation. As these cells express many innate immune receptors with the potential to directly recognize microbial or endogenous signals, we set out to assess whether their functions are locally influenced by the signals present at the onset of inflammation. Using a mouse model of peritonitis, we demonstrate that neutrophils elicited in the presence of C-type lectin receptor ligands have an increased ability to produce cytokines, chemokines, and lipid mediators in response to subsequent TLR stimulation. Importantly, we found that licensing of cytokine production was mediated by paracrine TNF-α-TNFR1 signaling rather than direct ligand sensing, suggesting a form of quorum sensing among neutrophils. Mechanistically, licensing was largely imparted by changes in the posttranscriptional regulation of inflammatory cytokines, whereas production of IL-10 was regulated at the transcriptional level. Altogether, our data suggest that neutrophils rapidly adapt their functions to the local inflammatory milieu. These phenotypic changes may promote rapid neutrophil recruitment in the presence of pathogens but limit inflammation in their absence.

PMID:
28219890
PMCID:
PMC5360520
DOI:
10.4049/jimmunol.1601465
[Indexed for MEDLINE]
Free PMC Article

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