Cutting Edge: Neutrophils License the Maturation of Monocytes into Effective Antifungal Effectors. Academic Article uri icon

Overview

abstract

  • Neutrophils are critical for the direct eradication of Aspergillus fumigatus conidia, but whether they mediate antifungal defense beyond their role as effectors is unclear. In this study, we demonstrate that neutrophil depletion impairs the activation of protective antifungal CCR2+ inflammatory monocytes. In the absence of neutrophils, monocytes displayed limited differentiation into monocyte-derived dendritic cells, reduced formation of reactive oxygen species, and diminished conidiacidal activity. Upstream regulator analysis of the transcriptional response in monocytes predicted a loss of STAT1-dependent signals as the potential basis for the dysfunction seen in neutrophil-depleted mice. We find that conditional removal of STAT1 on CCR2+ cells results in diminished antifungal monocyte responses, whereas exogenous administration of IFN-γ to neutrophil-depleted mice restores monocyte-derived dendritic cell maturation and reactive oxygen species production. Altogether, our findings support a critical role for neutrophils in antifungal immunity not only as effectors but also as important contributors to antifungal monocyte activation, in part by regulating STAT1-dependent functions.

publication date

  • October 10, 2022

Research

keywords

  • Monocytes
  • Neutrophils

Identity

PubMed Central ID

  • PMC10115354

Scopus Document Identifier

  • 85141892257

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.2200430

PubMed ID

  • 36216513

Additional Document Info

volume

  • 209

issue

  • 10