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

Immunity | Jun 20, 2017

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.

Pubmed ID: 28636955 RIS Download

Mesh terms: Animals | Antigens, Ly | Candida albicans | Candidiasis | Cells, Cultured | Disease Models, Animal | Humans | Immunotherapy | Interferon-gamma | Interleukin-15 | Kidney | Killer Cells, Natural | Lymphocyte Activation | Mice | Monocytes | Neutrophil Activation | Neutrophils | Spleen

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