Long-term effects of influenza A virus infections on lung cells and their response to pneumococci

Electron micrograph of coccal bacteria growing in chains — Electron micrograph of a pneumococcal strain. A total of over 90 pneumococcal serotypes are known to date. The image was taken as part of a cooperation with the department of Prof. Sven Hammerschmidt, University of Greifswald.

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07/04/2025

Immunological footprint shapes the defense against subsequent bacterial infections

Influenza viruses can trigger epigenetic changes in the alveolar epithelium, the cell layer that lines the alveoli, permanent changes in gene activity without changing the DNA itself. These changes have a lasting effect on subsequent immune responses and result in the body no longer being able to react appropriately to the bacterial pathogens in the event of a subsequent infection with pneumococci. A research team at the Helmholtz Centre for Infection Research (HZI) and the University Hospital Magdeburg (UMMD) has published new findings on the long-term consequences of an influenza A infection in a mouse model in the journal Cell Communication and Signaling.

The study, led by Prof. Dunja Bruder, researcher at the Institute of Medical Microbiology and Hospital Hygiene, UMMD, and head of the research group “Immune Regulation” at the HZI, shows that changes in the lung - especially in alveolar type II epithelial cells (AECII) - persist beyond virus elimination. AECII are central players in immune defense and tissue regeneration. The researchers investigated how surviving the flu influences their reaction to different pneumococcal serotypes. The study was conducted in close cooperation with the Department of Pneumology at the UMMD.

Dangerous secondary infection with pneumococci

As a result of influenza infection, the immune system reacts differently, which favors severe pneumonia caused by pneumococci. These are then often accompanied by excessive inflammation and can severely damage the lungs.

As part of the study, mice were first infected with the influenza A virus and then re-infected with different serotypes of the bacterium Streptococcus pneumoniae (pneumococci). The team analyzed both the bacterial spread in the lungs and the inflammatory reactions and changes at the AECII level.

The immunological changes were particularly clear in pneumococcal serotype 7F: following previous influenza infection, this triggered a pronounced inflammatory response with strong production of type I and type II interferons - messenger substances that activate the immune system. The AECII also showed epigenetic changes that influenced gene activity in the long term. This revealed that the lungs remain in an altered “alarm state” even after the virus has been eliminated.

group picture — Team around Prof. Dunja Bruder (from left): Prof. Dunja Bruder, Dr. Andreas Jeron, PD Sabine Stegemann-Koniszewski, Dr. Julia Boehme.

These results indicate that influenza leaves an “immunological footprint” in the lungs that shapes the defense against subsequent bacterial infections. “This phenomenon, known as ‘trained immunity’, describes the ability of cells to ‘remember’ previous infections and change their behavior based on this,” explain Dr. Julia Boehme and Dr. Andreas Jeron from Bruder's research group.

The study contributes to a better understanding of why certain pneumococcal serotypes can be particularly dangerous after influenza. Although over 90 serotypes are known, only a few cause invasive, life-threatening infections. Using a preclinical mouse model, Prof. Dunja Bruder's team was able to show for the first time how a survived influenza infection influences the reaction of alveolar type II epithelial cells to different pneumococcal serotypes. “In contrast to previous studies, which mostly investigated secondary infections during the acute influenza phase, our work shows that susceptibility to pneumococci also persists during the recovery phase - albeit primarily to invasive serotypes,” summarizes Bruder. The new findings on epigenetic and immunological changes in AECII provide valuable mechanistic clues as to how previous viral infections can impair the antibacterial defense capacity of the lungs in the long term - an aspect that could be important for the development of improved therapeutic and diagnostic approaches for bacterial superinfections in the long term.

Funding

The study was supported by the German Research Foundation (DFG) and the Helmholtz Association of German Research Centers (HGF).

Original press release

Original press release by the University Hospital Magdeburg (in German)

Original publication

Julia D Boehme, Andreas Jeron, Kristin Schultz, Lars Melcher, Katharina Schott, Elif Gelmez, Andrea Kröger, Sabine Stegemann-Koniszewski & Dunja Bruder. Epigenetic changes and serotype-specific responses of alveolar type II epithelial cells to Streptococcus pneumoniae in resolving influenza A virus infection. Cell Communication and Signaling (2025). DOI: 10.1186/s12964-025-02284-y