Browsing by Author "Reyes Servin, Jazmin"

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IFN Receptor 2 Regulates TNF-α–Mediated Damaging Inflammation during Aspergillus Pulmonary Infection
(The American Association of Immunologists, 2024-08) Rynda‐Apple, Agnieszka; Reyes Servin, Jazmin; Lenz, Julia; Roemer, Julia; Benson, Evelyn E.; Hall, Monica; Shepardson, Kelly M.
The increased incidence of invasive pulmonary aspergillosis, caused by Aspergillus fumigatus, occurring in patients infected with severe influenza or SARS-CoV-2, suggests that antiviral immune responses create an environment permissive to fungal infection. Our recent evidence suggests that absence of the type I IFN receptor 2 subunit (IFNAR2) of the heterodimeric IFNAR1/2 receptor is allowing for this permissive immune environment of the lung through regulation of damage responses. Because damage is associated with poor outcome to invasive pulmonary aspergillosis, this suggested that IFNAR2 may be involved in A. fumigatus susceptibility. In this study, we determined that absence of IFNAR2 resulted in increased inflammation, morbidity, and damage in the lungs in response to A. fumigatus challenge, whereas absence of IFNAR1 did not. Although the Ifnar2−/− mice had increased morbidity, we found that the Ifnar2−/− mice cleared more conidia compared with both wild-type and Ifnar1−/− mice. However, this early clearance did not prevent invasive disease from developing in the Ifnar2−/− mice as infection progressed. Importantly, by altering the inflamed environment of the Ifnar2−/− mice early during A. fumigatus infection, by neutralizing TNF-α, we were able to reduce the morbidity and fungal clearance in these mice back to wild-type levels. Together, our results establish a distinct role for IFNAR2 in regulating host damage responses to A. fumigatus and contributing to an A. fumigatus–permissive environment through regulation of inflammation. Specifically, our data reveal a role for IFNAR2 in regulating TNF-α–mediated damage and morbidity during A. fumigatus infection.