Article ; Online: Hierarchical effects of pro-inflammatory cytokines on the post-influenza susceptibility to pneumococcal coinfection.
2016 Volume 6, Page(s) 37045
Abstract: ... Although abundant pro-inflammatory responses have been reported as key contributing factors for these severe dual ... In the course of influenza A virus (IAV) infections, a secondary bacterial infection frequently ... infections, the relative contributions of cytokines remain largely unclear. In the current study ...
| Abstract | In the course of influenza A virus (IAV) infections, a secondary bacterial infection frequently leads to serious respiratory conditions provoking high hospitalization and death tolls. Although abundant pro-inflammatory responses have been reported as key contributing factors for these severe dual infections, the relative contributions of cytokines remain largely unclear. In the current study, mathematical modelling based on murine experimental data dissects IFN-γ as a cytokine candidate responsible for impaired bacterial clearance, thereby promoting bacterial growth and systemic dissemination during acute IAV infection. We also found a time-dependent detrimental role of IL-6 in curtailing bacterial outgrowth which was not as distinct as for IFN-γ. Our numerical simulations suggested a detrimental effect of IFN-γ alone and in synergism with IL-6 but no conclusive pathogenic effect of IL-6 and TNF-α alone. This work provides a rationale to understand the potential impact of how to manipulate temporal immune components, facilitating the formulation of hypotheses about potential therapeutic strategies to treat coinfections. |
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| MeSH term(s) | Animals ; Bacteremia/complications ; Bacteremia/microbiology ; Bacterial Load ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/microbiology ; Coinfection/immunology ; Coinfection/microbiology ; Coinfection/virology ; Computer Simulation ; Cytokines/physiology ; Disease Susceptibility ; Female ; Influenza A virus/immunology ; Influenza A virus/pathogenicity ; Lung/microbiology ; Macrophages, Alveolar/immunology ; Mice ; Mice, Inbred C57BL ; Models, Immunological ; Orthomyxoviridae Infections/complications ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/physiopathology ; Pneumonia, Pneumococcal/complications ; Pneumonia, Pneumococcal/etiology ; Pneumonia, Pneumococcal/immunology ; Streptococcus pneumoniae/immunology ; Streptococcus pneumoniae/pathogenicity ; Viral Load |
| Chemical Substances | Cytokines |
| Language | English |
| Publishing date | 2016-11-22 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/srep37045 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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