Rationale: Bacterial pneumonia leads to higher morbidity resulting in higher mortality and, consequently healthcare expenditures. Staphylococcus aureus, a gram-positive opportunistic bacterium that induces pneumonia, is common in both hospital-acquired and community-acquired infections. The increasing prevalence of multi-drug resistant strains such as Methicillin-Resistant Staphylococcus aureus (MRSA) has made treatment more challenging. Thus, alternative therapeutic interventions are warranted, including modulation of host defense to clear bacteria and to increase survival. Although the AIM2 inflammasome is a critical component of host defense against bacterial pathogens, its role in modulating innate and adaptive immune responses in S. aureus infection remains elusive. Therefore, we investigated whether AIM2 modulates the host defense against Staphylococcus aureus infection.

Methods: We used a murine model where both wild-type and knockout female mice of age 8-12 weeks were infected intratracheally with Staphylococcus aureus (5*10⁷ CFU/mice). After 12 and 24 hours, the mice were sacrificed to estimate the bacterial burden in lungs and extrapulmonary organs as well as cellular recruitment and cytokine profiles from Bronchoalveolar Lavage Fluid (BALF).

Results: Compared to wild-type mice, the AIM2 deficient mice displayed higher bacterial clearance from lungs and extrapulmonary organs. As expected, we found higher recruitment of macrophages and neutrophils in BALF of AIM2 knockout mice following MRSA infection. The level of IFN-γ was significantly higher in AIM2 deficient mice compared to wild-type mice suggesting its role in bacterial clearance and increasing host defense.

Conclusion: Taken together, these results suggest that AIM2 negatively regulates the host defense against MRSA-induced pneumonia. Therefore, inhibition of AIM2 inflammasome can be therapeutically beneficial in S. aureus-induced pneumonia.

Keywords: - AIM2, Staphylococcus aureus, Pneumonia