Differential type I IFN signaling is involved in regulating neutrophil anti-fungal host responses to Aspergillus fumigatus 3902

Abstract Description Invasive pulmonary aspergillosis (IPA), caused by the fungus Aspergillus fumigatus, generally occurs in patients with non-functioning immune systems. The recent rise in influenza and SARS-Cov-2-infected patients acquiring IPA suggests that anti-viral host responses, like type I IFNs, create an environment susceptible to fungal infection. We recently showed that absence of type I interferon receptor 2 (IFNAR) results in increased fungal clearance and damage during A. fumigatus infection compared to absence of IFNAR1. Currently, we are determining whether anti-fungal responses are involved in this. Here, we show that Ifnar2-/- PMNs killed significantly more conidia than Ifnar1-/- PMNs and this killing directly correlated with increased ROS levels. We next sought to determine the ROS response of the Ifnar2-/- PMNs to hyphae (Ifnar2-/- mice develop invasive disease) using bone-marrow (BM) derived PMNs. We found that Ifnar2-/- BM-PMNs had a faster and larger ROS burst in response to A. fumigatus hyphae compared to Ifnar1-/- and WT BM-PMNs. These results suggest that the ROS response of Ifnar2-/- PMNs may be dysregulated (hyperresponsive) and is involved in both the increased clearance and damage response occurring in the Ifnar2-/- mice during A. fumigatus infection. Together, our results expand our understanding of how anti-viral mechanisms, via IFNAR2 and IFNAR1, are creating a permissive environment for fungal infections to occur through regulation anti-fungal responses. Funding Sources Supported by NIH/NIAID K22AI153671. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)