CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis.

Macrophages facilitate critical functions in regulating pathogen clearance and immune homeostasis in tissues. The remarkable functional diversity exhibited by macrophage subsets is dependent on tissue environment and the nature of the pathological insult. Our current knowledge of the mechanisms that regulate the multifaceted counter-inflammatory responses mediated by macrophages remains incomplete. Here, we report that CD169+ macrophage subsets are necessary for protection under excessive inflammatory conditions. We show that in the absence of these macrophages, even under mild septic conditions, mice fail to survive and exhibit increased production of inflammatory cytokines. Mechanistically, CD169+ macrophages control inflammatory responses via interleukin-10 (IL-10), as CD169+ macrophage-specific deletion of IL-10 was lethal during septic conditions, and recombinant IL-10 treatment reduced lipopolysaccharide (LPS)-induced lethality in mice lacking CD169+ macrophages. Collectively, our findings show a pivotal homeostatic role for CD169+ macrophages and suggest they may serve as an important target for therapy under damaging inflammatory conditions. [Display omitted] • CD169+ macrophages provide critical regulatory cues to maintain immune homeostasis • CD169+ macrophages provide counter-inflammatory responses during sepsis by secreting IL-10 • The type of inflammatory stimuli serves as a rheostat for regulating macrophage polarization Yeung et al. investigate the mechanisms that regulate the multifaceted counter-inflammatory responses mediated by macrophages under inflammatory conditions. They show that the CD169+ macrophage subset is necessary for host survival even during mild septic conditions. The mechanism by which these macrophages impart the pivotal anti-inflammatory function is by secreting IL-10. [ABSTRACT FROM AUTHOR]