Defense mechanisms during respiratory infections in hosts with underlying asthma
| Autor: | Amali Samarasinghe, Kim LeMessurier, Meenakshi Tiwary |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:148.1-148.1 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.204.supp.148.1 |
| Popis: | Influenza can often be complicated by superinfections by bacteria such as Streptococcus pneumoniae. While these opportunistic bacterial pathogens do co-infect during seasonal influenza epidemics, the relationship is exaggerated during pandemic influenza virus infections as documented during all four previous influenza pandemics. Approximately 29–55% of hospitalized patients with Swine Flu with severe disease had a bacterial co-infection; however, asthmatics that were hospitalized during this influenza pandemic were less likely to have co-infections. We built a mouse model that recapitulated these intriguing epidemiologic findings that underlying asthma protected the host from severe morbidity and mortality associated with IAV and S. pneumoniae co-infection. These mice had significantly reduced bacterial load in the lungs, increased eosinophils and macrophages in the airways, but reduced tissue inflammation and scarring compared to non-allergic co-infected mice. We hypothesized that TH2-biased programming of eosinophils within the lungs of allergic mice heightened their immune responses to invading respiratory pathogens. We found that allergen sensitization and IAV exposure activated eosinophils marked by upregulation of CD69, ICAM-1, and IL-5Rα, maintained their viability, and enhanced bacterial uptake through receptor-mediated phagocytosis. Activated eosinophils prevented IAV-induced cytopathology on respiratory epithelia and were able to inhibit the growth and kill S. pneumoniae without undergoing cytolysis. Our data suggest a novel pathway by which eosinophils in hosts with asthma may protect the host from severe diseases induced by respiratory pathogens by inhibiting viral-bacterial synergy. |
| Databáze: | OpenAIRE |
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