Inflammatory Ly6Chigh Monocytes Protect against Candidiasis through IL-15-Driven NK Cell/Neutrophil Activation

Publication date: 20 June 2017
Source:Immunity, Volume 46, Issue 6
Author(s): Jorge Domínguez-Andrés, Lidia Feo-Lucas, María Minguito de la Escalera, Leticia González, María López-Bravo, Carlos Ardavín
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 Ly6C^high 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 Ly6C^high 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.

Graphical abstract

Teaser

The kidney is the main target organ in systemic C. albicans infection. Domínguez-Andrés et al. now show that effective defense against systemic candidiasis relies on type I interferon-dependent IL-15 production by spleen inflammatory monocytes, which drives splenic NK cell activation and GM-CSF release that in turn boost the candidacidal potential of kidney neutrophils.


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