Date of Graduation
Spring 2018
Degree
Master of Science in Biology
Department
Biology
Committee Chair
Christopher Lupfer
Abstract
Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically elevated during coinfection with IAV and S. pneumoniae. However, how IL-1β levels increase and their importance in coinfection is not known. We have discovered that IL-1β expression and secretion is increased during coinfection as a result of activation of multiple signaling pathways simultaneously. This was concluded in experiments where macrophages or mice deficient in various immune pathways including Myd88, Aim2 or Nlrp3 genes were examined for their effects on IL-1β production. Treatment options were then explored. Mice were given an antibiotic and/or an IL-1β neutralizing antibody. Treatment of mice with clindamycin antibiotic significantly improved mortality and simultaneously reduced IL-1β levels. Further inhibition of IL-1β using neutralizing antibodies resulted in improved weight gain compared to clindamycin alone. Thus, we concluded that IL-1β plays an important role during the coinfection of IAV and S. pneumoniae.
Keywords
: IL-1β, influenza A virus, S. pneumoniae, inflammasome, NF-κB, nod-like receptor (NLR).
Subject Categories
Bacterial Infections and Mycoses | Biology | Immunity | Immunology of Infectious Disease | Immunopathology | Medical Immunology | Other Immunology and Infectious Disease | Virus Diseases
Copyright
© Angeline E. Rodriguez
Recommended Citation
Rodriguez, Angeline E., "Enhanced Production of Pro-IL-1Βeta Contributes to Immunopathology during the Coinfection of Influenza a Virus and Streptococcus Pneumoniae" (2018). MSU Graduate Theses/Dissertations. 3242.
https://bearworks.missouristate.edu/theses/3242
Open Access
Included in
Bacterial Infections and Mycoses Commons, Biology Commons, Immunity Commons, Immunology of Infectious Disease Commons, Immunopathology Commons, Medical Immunology Commons, Other Immunology and Infectious Disease Commons, Virus Diseases Commons
