Grant: CIHR Fellowship

A clinical entity termed the "obesity paradox" suggests that overweight individuals (BMI>25) are 20-30% more likely to survive hospitalized pneumonia. There are two ways to survive an infection. The first depends on resistance mechanisms that kill the pathogen creating an arms race between the host and pathogen that can lead to pathogen resistance, immunopathology, and mortality. The second is a distinct defense classification called the co-operative defense system. The co-operative defense system encodes disease tolerance mechanisms that prevent or alleviate pathology generated during infection without affecting pathogen number nor fitness. The role of tolerance in the obesity paradox is unknown. Legionella pneumophila (Lp) is a bacterial pathogen that infects and resides in immune cells of the lung. Preliminary data has identified that host utilization of fatty acids is critical for defenses and survival against Lp. These data suggest that an increased abundance of circulating fatty acids may improve host outcome to infection. I hypothesize that fat promotes host defenses during Lp infection through fatty acid release and availability for utilization by the host. This project will determine how host adipose composition and fatty acid availability effects tolerance defense mechanisms toward Lp lung infection. I will identify specific host immune or metabolic pathways that benefit from the increased abundance of fat and fatty acids that promote host health during infection. Discovering new disease tolerance mechanisms is critical for overcoming resistance in pathogens, creating new avenues to treat infectious diseases.