Influenza A virus (IAV) and secondary bacterial infections (SBI) are responsible for a significant number of illnesses and deaths each year. Management of these diseases is difficult, in part due to a lack of understanding of complex interplay of host-pathogen interactions and inability to study pneumonia in clinical settings. To advance the goal of developing effective therapeutics and predicting IAV and SBI risk, new microbiologic tools that can assess how host immune responses work to limit viral burden and enhance bacterial invasion in quantitative detail is essential. This project addresses gaps in immunological knowledge of IAV and SBIs and gaps in developing predictive models and interpreting infection data by using a tandem mathematical-experimental approach to quantify alveolar macrophage loss (Aim 1) and SBI related type I interferon exacerbation (Aim 2). These studies will exploit the predictive models to establish the intricate feedbacks in these responses, identify controlling parameters and dynamics that govern different clinical outcomes, improve interpretation of immunological and clinical data, and reveal new targets for treatment and prevention of influenza and related bacterial infections.

Public Health Relevance

Influenza A Virus infection and the bacterial infections that complicate influenza pose considerable public health threats by causing widespread morbidity and mortality. Advancing the availability of effective therapeutic agents to combat disease is necessary, but knowledge of how the host immune responses are regulated and work to control the pathogens is limited. The objective of the proposed research is to quantify the effect of two innate immune responses in limiting viral burden, enhancing disease, and facilitating bacterial invasion during influenza by developing and validating novel predictive mathematical models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI139088-02
Application #
9716551
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Lane, Mary Chelsea
Project Start
2018-07-01
Project End
2023-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38103