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Innate immune responses at the asymptomatic stage of influenza A viral infections of Streptococcus pneumoniae colonized and non-colonized mice.

ABSTRACT: Seasonal Influenza A virus (IAV) infections can promote dissemination of upper respiratory tract commensals such as Streptococcus pneumoniae to the lower respiratory tract resulting in severe life-threatening pneumonia. Here, we aimed to compare innate immune responses in the lungs of healthy colonized and non-colonized mice after IAV challenge at the initial asymptomatic stage of infection. Responses during a severe bacterial pneumonia were profiled for comparison. Cytokine and innate immune cell imprints of the lungs were analyzed. Irrespective of the colonization status, mild H1N1 IAV infection was characterized by a bi-phasic disease progression resulting in full recovery of the animals. Already at the asymptomatic stage of viral infection, the pro-inflammatory cytokine response was as high as in pneumococcal pneumonia. Flow cytometry analyses revealed an early influx of inflammatory monocytes into the lungs. Neutrophil influx was mostly limited to bacterial infections. The majority of cells, except monocytes, displayed an activated phenotype characterized by elevated CCR2 and MHCII expression. In conclusion, we show that IAV challenge of colonized healthy mice does not automatically result in severe co-infection. However, a general local inflammatory response was noted at the asymptomatic stage of infection irrespective of the infection type.

SUBMITTER: Cuypers F

PROVIDER: S-EPMC8523748 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Innate immune responses at the asymptomatic stage of influenza A viral infections of Streptococcus pneumoniae colonized and non-colonized mice.

Cuypers Fabian F Schäfer Alexander A Skorka Sebastian B SB Surabhi Surabhi S Tölken Lea A LA Paulikat Antje D AD Kohler Thomas P TP Otto Saskia A SA Mettenleiter Thomas C TC Hammerschmidt Sven S Blohm Ulrike U Siemens Nikolai N

Scientific reports 20211018 1

Seasonal Influenza A virus (IAV) infections can promote dissemination of upper respiratory tract commensals such as Streptococcus pneumoniae to the lower respiratory tract resulting in severe life-threatening pneumonia. Here, we aimed to compare innate immune responses in the lungs of healthy colonized and non-colonized mice after IAV challenge at the initial asymptomatic stage of infection. Responses during a severe bacterial pneumonia were profiled for comparison. Cytokine and innate immune ce ...[more]

PMID: 34663857

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Project description:Streptococcus pneumoniae and influenza A virus (IAV) are significant agents of pneumonia cases and severe respiratory infections globally. Secondary bacterial infections, particularly by Streptococcus pneumoniae, are common in IAV-infected individuals, leading to critical outcomes. Despite reducing mortality, pneumococcal vaccines have high production costs and are serotype specific. The emergence of new circulating serotypes has led to the search for new prevention strategies that provide a broad spectrum of protection. In this context, vaccination using antigens present in all serotypes, such as Pneumococcal Surface Protein A (PspA), can offer broad coverage regardless of serotype. Employing the reverse genetics technique, our research group developed a recombinant influenza A H1N1 virus that expresses PspA (Flu-PspA), through the replacement of neuraminidase by PspA. This virus was evaluated as a bivalent vaccine against infections caused by influenza A and S. pneumoniae in mice. Initially, we evaluated the Flu-PspA virus's ability to infect cells and express PspA in vitro, its capacity to multiply in embryonated chicken eggs, and its safety when inoculated in mice. Subsequently, the protective effect against influenza A and Streptococcus pneumoniae lethal challenge infections in mice was assessed using different immunization protocols. Analysis of the production of antibodies against PspA4 protein and influenza, and the binding capacity of anti-PspA4 antibodies/complement deposition to different strains of S. pneumoniae were also evaluated. Our results demonstrate that the Flu-PspA virus vaccine efficiently induces PspA protein expression in vitro, and that it was able to multiply in embryonated chicken eggs even without exogenous neuraminidase. The Flu-PspA-based bivalent vaccine was demonstrated to be safe, stimulated high titers of anti-PspA and anti-influenza antibodies, and protected mice against homosubtypic and heterosubtypic influenza A and S. pneumoniae challenge. Moreover, an efficient binding of antibodies and complement deposition on the surface of pneumococcal strains ascribes the broad-spectrum vaccine response in vivo. In summary, this innovative approach holds promise for developing a dual-protective vaccine against two major respiratory pathogens.

Dataset Information

Innate immune responses at the asymptomatic stage of influenza A viral infections of Streptococcus pneumoniae colonized and non-colonized mice.

Publications

Innate immune responses at the asymptomatic stage of influenza A viral infections of Streptococcus pneumoniae colonized and non-colonized mice.

Similar Datasets

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