Dr. Jake Mayfield awarded a Faculty Research Grant

Dr. Jake Mayfield

More than 100 different microbes are known to cause pneumonia. Of those, Histoplasma capsulatum is the most common cause of fungal pneumonia worldwide, responsible for both isolated infections and outbreaks.  Severe cases require antifungal therapy for survival.  The Faculty Research Grant will fund research that seeks to characterize how the mammalian immune system detects the fungus that causes histoplasmosis and to better understand why Histoplasma capsulatum causes disease.

While host genetics and exposure level clearly influence the severity of pneumonia, both ultimately exert their influence on the immune response. Therefore, determining immune cell types and molecular events that lead to improved disease outcomes is critical to developing better control strategies. Dr. Mayfield's research seeks to define the initial interaction between H. capsulatum and the immune system, with the long-term goal of understanding how severe or lethal disease occurs despite an otherwise robust immune response.

The cell surface protein ITGAM (integrin alpha M; CD11b, Mac-1) was previously shown to interact with H. capsulatum, serving as a receptor for yeast recognition and internalization. However, Dr. Mayfield's research demonstrated that genetic disruption of the gene Itgam significantly worsened histoplasmosis outcome, but simultaneously improved the inflammatory immune response. The experiments in the proposed research test hypotheses that could explain the conflicting data. In particular, my central hypothesis is that ITGAM generates previously a regulatory signal that dampens the immune response to histoplasmosis. This will be tested using microscopy to observe yeast internalization, inhibitors to block ITGAM signaling, and immune assays to measure the immune response.