Dysregulated pulmonary inflammatory responses exacerbate the outcome of secondary aspergillosis following influenza

• Published in: mBio Vol. 14; no. 5; p. e0163323
• Main Authors: Lee, Chrono K, Oliveira, Lorena V N, Akalin, Ali, Specht, Charles A, Lourenco, Diana, Gomez, Christina L, Ramirez-Ortiz, Zaida G, Wang, Jennifer P, Levitz, Stuart M
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 31.10.2023
• Subjects: Animals; aspergillosis; Aspergillosis - microbiology; Aspergillus fumigatus; fungal immunology; Humans; Inflammation - complications; influenza; Influenza, Human - complications; Invasive Pulmonary Aspergillosis - microbiology; Lung - microbiology; Mice; mouse models of infection; Mycology; Pulmonary Aspergillosis; Research Article; superinfection; influenza; superinfection; fungal immunology; mouse models of infection; aspergillosis
• ISSN: 2150-7511; 2150-7511
• DOI: 10.1128/mbio.01633-23

Severe influenza is a risk factor for fatal invasive pulmonary aspergillosis; however, the mechanistic basis for the lethality is unclear. Utilizing an influenza-associated pulmonary aspergillosis (IAPA) model, we found that mice infected with influenza A virus followed by had 100% mortality when superinfected during the early stages of influenza but survived at later stages. While superinfected mice had dysregulated pulmonary inflammatory responses compared to controls, they had neither increased inflammation nor extensive fungal growth. Although influenza-infected mice had dampened neutrophil recruitment to the lungs following subsequent challenge with , influenza did not affect the ability of neutrophils to clear the fungi. Our data suggest that the lethality seen in our model of IAPA is multifactorial with dysregulated inflammation being a greater contributor than uncontrollable microbial growth. If confirmed in humans, our findings provide a rationale for clinical studies of adjuvant anti-inflammatory agents in the treatment of IAPA.