IL-1α and IL-1β play non-redundant roles in limiting in vivo Aspergillus fumigatus pulmonary growth (P3092)

Abstract

Abstract Aspergillus fumigatus is a mold that causes severe pulmonary infections in humans, such as invasive pulmonary Aspergillosis (IPA). Currently, our knowledge of how A. fumigatus growth is controlled in the respiratory tract is limited. Phagocytic alveolar macrophages constitute the first line of defense against inhaled A. fumigatus conidia; subsequently, neutrophils and macrophages are sequentially recruited to the respiratory tract to control fungal growth and germination . But how neutrophils and macrophages are recruited to the respiratory tract after A. fumiguatus infection remains ill defined. During sterile inflammation early neutrophil recruitment is dependent on IL-1α, while late macrophage recruitment is dependent on IL-1β. A. fumigatus infection induced the expression of both IL-1α and IL-1β. However, IL-1R1- and ASC-deficient mice displayed differential susceptibility to IPA. IL-1R1-deficient mice were highly susceptible to A. fumigatus infection as measured by increases in fungal growth, lung tissue damage, and fungal dissemination. In contrast, ASC-deficient mice were only mildly susceptible to A. fumigatus infection. IL-1R1- and ASC-deficient mice displayed a severe defect in neutrophil recruitment during the first 48h and a defect in macrophage recruitment after 48h, respectively. Taken together, our data reveal important non-redundant roles for the IL-1α and IL-1β in controlling A. fumigatus infection in the lung.