Modulating MAVS Aggregation to Promote Host Resilience During Bacterial Pneumonia

Our proposal is focused on the Mitochondria Antiviral Signaling (MAVS) pathway, as a key contributor to the impaired host tolerance by causing pathological inflammatory and injury response during bacterial lung infections. The goal of our study is to gain in depth understanding of MAVS regulatory mechanisms during bacterial infection and find optimal therapeutic options that limit MAVS and promote host tolerance or resilience during pulmonary bacterial infections. We hypothesize that MAVS aggregation contributes to uncontrolled inflammatory and cell death responses leading to exacerbated tissue injury. Our aims are the following: to characterize MAVS aggregation, its disaggregation and impact on host pathological response during bacterial lung infection, To investigate mechanisms that limit MAVS-mediated dysregulation of host resilience to limit pathologic consequences of Pseudomonas infection, and to determine the clinical and biological relevance of the MAVS aggregation and its regulation by PINK1 in patients with bacterial pneumonia. The ultimate goal is to develop new and viable therapeutic strategies to regulate MAVS response during the bacterial infection to help the host better deal with the infections by limiting pathological inflammation without compromising the bacterial clearance.