Semester of Graduation
Master of Science (MS)
Bacterial pneumonia is the leading cause of death in children under the age of five, claiming the lives of two million children each year. Staphylococcus aureus is the extracellular Gram-positive bacteria that causes necrotizing pneumonia. Moreover, the spread of antibiotic-resistant and hypervirulent strains has made treatment more challenging. Absent in melanoma 2 (AIM2) is a dsDNA-sensing cytosolic innate immune receptor that activates inflammasomes and is crucial for host defense against intracellular bacteria and DNA viruses. However, its role in extracellular bacterial pathogen-induced pneumonia is unclear. Therefore, understanding how AIM2 initiates host responses during Staphylococcus aureus is crucial for the development of novel therapeutics as well as prevention strategies.
To investigate more about how the AIM2 inflammasomes regulate host defense against S. aureus infection, we used C57BL6 (wild-type) and AIM2 gene-deficient (AIM2-/-) mice in an S. aureus-induced pneumonia model. In this model, AIM2-/- mice exhibit lower bacterial counts in lungs, BALF, and extrapulmonary organs (liver and spleen) compared to wild-type (WT) mice. In addition, there was an increase in immune cells (neutrophils and macrophages) in BALF of AIM2-/- mice compared to WT. Pro-inflammatory cytokines, including IFN-γ and TNF-α, were also found to be increased in AIM2-/- mice; however, interestingly, IL-6 was found to be lower in AIM2-/- mice than in WT. Further, an intracellular killing experiment revealed that AIM2-/- bone marrow macrophages and neutrophils have an increased ability to clear bacteria compared to their WT counterparts. These findings suggest that the AIM2 inflammasome has a negative regulatory role in S. aureus-induced pneumonia.
Dhakal, Bibek, "Role of AIM2 Inflammasome in Pulmonary Host Defense Against Staphylococcus aureus-induced Pneumonia" (2021). LSU Master's Theses. 5456.