Faculty Affairs and Academic Programs
Juliet Morrison
Life Sciences; Agriculture and Veterinary Sciences
Microbiology and Plant Pathology
UCLA
Exploring Serosal Macrophages as Tools to Treat Viral Lung Infections
There is an urgent need for new therapies to alleviate the burden of lung infection, the 4th leading cause of global death. Understanding how immune cell populations promote or resolve lung infection, inflammation and damage can identify specific cellular targets for therapeutic intervention. This proposal stems from our recent discovery of a novel lung macrophage population that originates in the pleural cavity and whose presence promotes resolution of influenza. Pleural macrophages (PMs) have been explored in pleural diseases such as mesothelioma and pleurisy, but not in lung diseases such as pneumonia. That macrophages enter the lungs via an extravascular route to promote tissue recovery is paradigm shifting. The communication between the lung and its serosal cavity is an exciting new area of study. As such, our novel finding opens several new avenues of research. Ultimately, we plan to capitalize on our fundamental discoveries to harness serosal macrophages, specifically pleural and peritoneal macrophages, as therapeutics for lung and pleural cavity diseases. This will be accomplished with the following Specific Aims. In Aim 1, we will identify commonalities and differences in PM translocation and function in response to infection with seasonal and avian influenza viruses, as well as SARS-CoV-2. In Aim 2, we will identify the transcriptomic drivers of PM translocation and PM-mediated recovery from lung infections. In Aim 3, we will measure the impacts of in vivo and ex vivo PM manipulation on infection outcomes. In Aim 4, we will explore the effect of the pleural cavity niche on the phenotypes and transcriptional profiles of transplanted peritoneal macrophages.
