S3.3c Alveolar macrophage-mediated host resistance against Aspergillus fumigatus

S3.3 INNATE IMMUNE RESPONSES TO PATHOGENIC FUNGI, SEPTEMBER 21, 2022, 4:45 PM - 6:15 PM: : Alveolar macrophages (AlvMφ) reside on the luminal surface of the airways serving as the primary phagocyte within the airways of the lungs where they act as immune sentinel cells sensing and responding to microbial and environmental exposures. In this role, AlvMφ must be able to respond in a manner that is appropriate to the threat posed which has been hypothesized to occur through sensing microbial vitality and/or patterns of pathogenesis. It is well-established that AlvMφ interact with phagocytose and respond to A. fumigatus, but their role in host resistance against A. fumigatus is currently controversial. Here I will discuss the role of AlvMφ play in orchestrating a robust and effective antifungal innate immune response to mediate A. fumigatus clearance. AlvMφ orchestrate the protective innate immune response against A. fumigatus by sensing live fungal conidia using the cytosolic RNA-sensing MDA5 receptor to initiate the host protective type I and type III interferon response in both mice and humans. The activation of MDA5/MAVS signaling appears to be mediated by both fungal dsRNA-dependent and fungal dsRNA-independent mechanisms. Thus, AlvMφ serve as a central hub for regulating and tuning the antifungal immune response within the respiratory tract.