IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis

Abstract Viral infections increase host susceptibility to opportunistic pathogens like Aspergillus fumigatus (AF), exacerbating disease severity and prolonging its clinical course. Interleukin‐6 (IL‐6) drives pathological inflammation in viral infections such as COVID‐19, but its role in influenza,...

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Main Authors: Lokesh Sharma, Ravineel B. Singh, Nathaniel J. Tolman, Caden Ngeow, Alexis M. Duray, Nima Naghshtabrizi, Aijaz Ahmad, William Bain, Keven M. Robinson
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Physiological Reports
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Online Access:https://doi.org/10.14814/phy2.70372
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Summary:Abstract Viral infections increase host susceptibility to opportunistic pathogens like Aspergillus fumigatus (AF), exacerbating disease severity and prolonging its clinical course. Interleukin‐6 (IL‐6) drives pathological inflammation in viral infections such as COVID‐19, but its role in influenza, particularly with secondary AF infection, remains unclear. Using a mouse model of post‐influenza AF infection, including IL‐6 knockout mice, we found that IL‐6 signaling promotes neutrophilic lung inflammation but is not required for pathogen clearance of either influenza or AF. However, IL‐6 deficiency increases epithelial cell damage, as indicated by elevated RAGE levels in bronchoalveolar lavage fluid. In contrast, lung capillary permeability (measured by IgM levels in BAL) and tissue injury (assessed histologically) remain unaffected in the absence of IL‐6 signaling. These findings reveal a nuanced role for IL‐6 in post‐influenza AF infection, underscoring its contribution to lung inflammation and epithelial integrity.
ISSN:2051-817X