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,...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-05-01
|
| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.70372 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849233655463936000 |
|---|---|
| author | Lokesh Sharma Ravineel B. Singh Nathaniel J. Tolman Caden Ngeow Alexis M. Duray Nima Naghshtabrizi Aijaz Ahmad William Bain Keven M. Robinson |
| author_facet | Lokesh Sharma Ravineel B. Singh Nathaniel J. Tolman Caden Ngeow Alexis M. Duray Nima Naghshtabrizi Aijaz Ahmad William Bain Keven M. Robinson |
| author_sort | Lokesh Sharma |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ecf92d24e1aa46d8a52eb1a01d5dbffe |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-ecf92d24e1aa46d8a52eb1a01d5dbffe2025-08-20T04:27:55ZengWileyPhysiological Reports2051-817X2025-05-011310n/an/a10.14814/phy2.70372IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosisLokesh Sharma0Ravineel B. Singh1Nathaniel J. Tolman2Caden Ngeow3Alexis M. Duray4Nima Naghshtabrizi5Aijaz Ahmad6William Bain7Keven M. Robinson8Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary Medicine, Department of Pediatrics University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USAAbstract 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.https://doi.org/10.14814/phy2.70372aspergillusIL‐6 signalinginflammationinfluenzainfluenza associated pulmonary aspergillosis |
| spellingShingle | Lokesh Sharma Ravineel B. Singh Nathaniel J. Tolman Caden Ngeow Alexis M. Duray Nima Naghshtabrizi Aijaz Ahmad William Bain Keven M. Robinson IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis Physiological Reports aspergillus IL‐6 signaling inflammation influenza influenza associated pulmonary aspergillosis |
| title | IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis |
| title_full | IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis |
| title_fullStr | IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis |
| title_full_unstemmed | IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis |
| title_short | IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis |
| title_sort | il 6 signaling regulates the inflammatory response without impacting pathogen burden during influenza associated pulmonary aspergillosis |
| topic | aspergillus IL‐6 signaling inflammation influenza influenza associated pulmonary aspergillosis |
| url | https://doi.org/10.14814/phy2.70372 |
| work_keys_str_mv | AT lokeshsharma il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis AT ravineelbsingh il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis AT nathanieljtolman il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis AT cadenngeow il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis AT alexismduray il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis AT nimanaghshtabrizi il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis AT aijazahmad il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis AT williambain il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis AT kevenmrobinson il6signalingregulatestheinflammatoryresponsewithoutimpactingpathogenburdenduringinfluenzaassociatedpulmonaryaspergillosis |