Flu ACHOO! Modelling the immune response to influenza-bacterial coinfection

12 Jul 2018, 10:30
New Law School/--028 (University of Sydney)

New Law School/--028

University of Sydney

Oral Presentation Minisymposium: Immunology and Infection Subgroup Immunobiology and infection subgroup


Dr Amber Smith (University of Tennessee Health Science Center)


Influenza A virus (IAV) infections are often complicated by bacterial pathogens like Streptococcus pneumoniae (SP, pneumococcus), which have accounted for 40-95% of IAV-associated mortality. IAV-SP coinfection is characterized by rapid, uncontrolled bacterial growth, a rebound in viral titers, and a robust inflammatory response. Several factors contribute to influenza-pneumococcal pathogenicity, including aberrant immune responses, tissue destruction, and pathogen strain and dose. To determine the contribution, regulation, and time-scales of different mechanisms, we analyze infection kinetics with mathematical models then experimentally validate our model predictions. Through this model-experiment exchange, we have identified how virus induced alveolar macrophage (AM) depletion dictates bacterial establishment and initial growth kinetics, and that bacteria enhance virus replication efficiency by blocking interferon (IFN) signalling. Because additional mechanisms may contribute to the development of pneumonia in coinfected animal, we infected mice with IAV then SP at different times post-influenza and simultaneously measured numerous variables. Modelling these data suggests that new infections contribute to the viral rebound, that suppressed T cell responses and exacerbated IFN responses have little impact, that the increased AM depletion is bacterial mediated. Collectively, our models and data provide insight into the mechanisms of IAV-SP coinfection, demonstrate the accuracy and predictive power of theoretical models, and highlight the importance of validating model predictions.

Primary author

Dr Amber Smith (University of Tennessee Health Science Center)

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