Influenza A Virus Exacerbates Group A Streptococcus Infection and Thwarts Anti-Bacterial Inflammatory Responses in Murine Macrophages
2022
Aleith, Johann | Brendel, Maria | Weipert, Erik | Müller, Michael | Schultz, Daniel | Group, Ko-Infekt Study | Müller-Hilke, Brigitte | Methling, Karen | Lalk, Michael | Blohm, Ulrike | Schäfer, Alexander | Kreikemeyer, Bernd
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.
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Bibliographic information
Publisher MDPI (Multidisciplinary Digital Publishing Institute)
ISSN 2076-0817Publisher Cold Spring Harbor Laboratory
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