title: Hierarchical effects of pro-inflammatory cytokines on the post-influenza susceptibility to pneumococcal coinfection.
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.
authors.affiliation: Infection Immunology Group, Institute of Medical Microbiology, Disease Prevention and Control, Otto-von-Guericke University Magdeburg, Germany.|Systems Medicine of Infectious Disease Group, Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Chair for Automation/Modeling, Institute for Automation Engineering, Otto-von-Guericke University Magdeburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Duvigneau
authors.affiliation: Infection Immunology Group, Institute of Medical Microbiology, Disease Prevention and Control, Otto-von-Guericke University Magdeburg, Germany.|Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Niharika
authors.initials: N
authors.lastname: Sharma-Chawla
authors.affiliation: Systems Medicine of Infectious Disease Group, Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Boianelli
authors.affiliation: Infection Immunology Group, Institute of Medical Microbiology, Disease Prevention and Control, Otto-von-Guericke University Magdeburg, Germany.|Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegemann-Koniszewski
authors.affiliation: Systems Medicine of Infectious Disease Group, Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Van Kinh
authors.initials: VK
authors.lastname: Nguyen
authors.affiliation: Infection Immunology Group, Institute of Medical Microbiology, Disease Prevention and Control, Otto-von-Guericke University Magdeburg, Germany.|Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
authors.affiliation: Systems Medicine of Infectious Disease Group, Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Esteban A
authors.initials: EA
authors.lastname: Hernandez-Vargas
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000150:complications / Q000382:microbiology; D058491:Bacterial Load; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000382:microbiology; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D003198:Computer Simulation; D016207:Cytokines / Q000502:physiology*; D004198:Disease Susceptibility; D005260:Female; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity*; D008168:Lung / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000209:etiology / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D019562:Viral Load
chemical_list: D016207:Cytokines