Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary <i>Aspergillus fumigatus</i> Infection by Regulating Natural Killer Cell Survival

Abstract

&lt;i&gt;Aspergillus fumigatus&lt;/i&gt; is a ubiquitous, yet potentially pathogenic, mold. The immune system employs innate receptors, such as dectin-1, to recognize fungal pathogens, but the immunological networks that afford protection are poorly explored. Here, we investigated the role of dectin-1 in anti-&lt;i&gt;A. fumigatus&lt;/i&gt; response in an experimental model of acute invasive aspergillosis. Mice lacking dectin-1 presented enhanced signs of inflammation, with increased production of inflammatory cytokines and neutrophil infiltration, quickly succumbing to the infection. Curiously, resistance did not require T/B lymphocytes or IL-17. Instead, the main effector function of dectin-1 was the preservation of the NK cell population in the kidneys by the provision of the cytokine IL-15. While the depletion of NK cells impaired host defense in wild-type mice, IL-15 administration restored antifungal responses in dectin-1-deficient mice. Our results uncover a new effector mechanism for dectin-1 in anti-&lt;i&gt;Aspergillus&lt;/i&gt; defense, adding an alternative approach to understand the pathophysiology of this infection.