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

## TL;DR

This study shows that IL-6 signaling increases lung inflammation during a secondary fungal infection after influenza, but does not affect pathogen levels or overall lung damage.

## Contribution

The study reveals a specific role for IL-6 in promoting inflammation and epithelial damage during post-influenza Aspergillus fumigatus infection in mice.

## Key findings

- IL-6 signaling promotes neutrophilic lung inflammation but is not needed for clearing influenza or Aspergillus fumigatus.
- IL-6 deficiency leads to increased epithelial cell damage, as shown by elevated RAGE levels in bronchoalveolar lavage fluid.
- Lung capillary permeability and tissue injury are not affected by the absence of IL-6 signaling.

## 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.