Immunity
Volume 46, Issue 6, 20 June 2017, Pages 1059-1072.e4
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Article
Inflammatory Ly6Chigh Monocytes Protect against Candidiasis through IL-15-Driven NK Cell/Neutrophil Activation

https://doi.org/10.1016/j.immuni.2017.05.009Get rights and content
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Highlights

  • NK cell and neutrophil activation during C. albicans infection requires IL-15

  • Inflammatory Ly6Chigh monocytes are the main source of IL-15 in response to C. albicans infection

  • Type I IFN controls C. albicans-induced IL-15 production by inflammatory monocytes

  • Defense against systemic candidiasis requires spleen-kidney cooperative immunity

Summary

Neutrophils play a crucial role in defense against systemic candidiasis, a disease associated with a high mortality rate in patients receiving immunosuppressive therapy, although the early immune mechanisms that boost the candidacidal activity of neutrophils remain to be defined in depth. Here, we used a murine model of systemic candidiasis to explore the role of inflammatory Ly6Chigh monocytes in NK cell-mediated neutrophil activation during the innate immune response against C. albicans. We found that efficient anti-Candida immunity required a collaborative response between the spleen and kidney, which relied on type I interferon-dependent IL-15 production by spleen inflammatory Ly6Chigh monocytes to drive efficient activation and GM-CSF release by spleen NK cells; this in turn was necessary to boost the Candida killing potential of kidney neutrophils. Our findings unveil a role for IL-15 as a critical mediator in defense against systemic candidiasis and hold promise for the design of IL-15-based antifungal immunotherapies.

Keywords

Candidiasis
IL-15
type I interferon
GM-CSF
monocytes
NK cells
neutrophils

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