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Updated: Jul 8, 2026
Using Bioluminescent Imaging to Investigate Synergism Between Streptococcus pneumoniae and Influenza A Virus in Infant Mice
Published on: April 14, 2011
Influenza A Virus Exacerbates Group A Streptococcus Infection and Thwarts Anti-Bacterial Inflammatory Responses in
Johann Aleith1, Maria Brendel1, Erik Weipert1
1Core Facility for Cell Sorting and Cell Analysis, Rostock University Medical Center, 18057 Rostock, Germany.
Abstract:
Seasonal influenza epidemics pose a considerable hazard for global health. In the past decades, accumulating evidence revealed that influenza A virus (IAV) renders the host vulnerable to bacterial superinfections which in turn are a major cause for morbidity and mortality. However, whether the impact of influenza on anti-bacterial innate immunity is restricted to the vicinity of the lung or systemically extends to remote sites is underexplored. We therefore sought to investigate intranasal infection of adult C57BL/6J mice with IAV H1N1 in combination with bacteremia elicited by intravenous application of Group A Streptococcus (GAS). Co-infection in vivo was supplemented in vitro by challenging murine bone marrow derived macrophages and exploring gene expression and cytokine secretion. Our results show that viral infection of mice caused mild disease and induced the depletion of CCL2 in the periphery. Influenza preceding GAS infection promoted the occurrence of paw edemas and was accompanied by exacerbated disease scores. In vitro co-infection of macrophages led to significantly elevated expression of TLR2 and CD80 compared to bacterial mono-infection, whereas CD163 and CD206 were downregulated. The GAS-inducible upregulation of inflammatory genes, such as Nos2, as well as the secretion of TNFα and IL-1β were notably reduced or even abrogated following co-infection. Our results indicate that IAV primes an innate immune layout that is inadequately equipped for bacterial clearance.
Insights
Influenza A virus (IAV) infection impairs the body's ability to fight bacterial infections, even in distant sites. This viral priming leaves the innate immune system poorly equipped for bacterial clearance, increasing disease severity.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Seasonal influenza epidemics are a global health concern.
- Influenza A virus (IAV) infections increase susceptibility to secondary bacterial infections, a major cause of illness and death.
- The systemic impact of influenza on anti-bacterial innate immunity beyond the lungs is not well understood.
Purpose of the Study:
- To investigate the systemic effects of influenza A virus (IAV) on innate immunity against bacterial superinfections.
- To determine if IAV infection compromises the host's ability to clear bacteria from remote sites.
Main Methods:
- Adult C57BL/6J mice were intranasally infected with IAV H1N1.
- Bacteremia was induced by intravenous injection of Group A Streptococcus (GAS).
- Murine bone marrow-derived macrophages were co-infected in vitro to analyze gene expression and cytokine secretion.
Main Results:
- IAV infection led to mild disease and reduced peripheral CCL2 levels.
- Concurrent influenza and GAS infection resulted in exacerbated disease scores and paw edema.
- In vitro, IAV-GAS co-infected macrophages showed increased TLR2 and CD80 expression, and decreased CD163 and CD206.
- GAS-induced inflammatory gene expression (Nos2) and cytokine secretion (TNFα, IL-1β) were reduced in co-infected macrophages.
Conclusions:
- IAV infection alters the innate immune landscape, making it less effective against bacterial pathogens.
- The systemic impact of influenza compromises the immune system's capacity for bacterial clearance.
- These findings highlight the critical interplay between viral and bacterial infections in host defense.
