Macrophages from biological males and females are differentially activated after infection with Cryptococcus neoformans 9104

Abstract Description Introduction Cryptococcus neoformans is a fungal pathogen responsible for causing respiratory infections and fungal meningitis, affecting predominantly males and immunocompromised individuals. In response to an infection, macrophages undergo classical (M1) or alternative (M2) activation. Classically activated macrophages are pro-inflammatory, responsible for killing pathogens, and produce nitric oxide (NO). Alternatively activated macrophages are anti-inflammatory, function to clear inflammation and repair tissue, and produce arginase. Objective: This study measured nitric oxide and arginase production in macrophages isolated from male and female blood donors in response to C. neoformans infection. Methods Macrophages were differentiated from blood samples of biological male and female donors using GM-CSF and then infected with C. neoformans for 48 h. Media collected from the 6, 24, and 48 h time points were tested for nitric oxide and arginase production. Results At 48 h female macrophages showed an M1 phenotype, as evidenced by significantly elevated NO levels, while male macrophages showed an M2 phenotype, as evidenced by significantly elevated arginase levels. Conclusions These findings suggest that there are different macrophage phenotypes in response to C. neoformans infection between males and females. These differences likely affect the immune response and susceptibility to C. neoformans and may help explain why males are predominantly affected. Funding Sources This research was supported by a Marian University Wood College of Osteopathic Medicine (MU-WCOM) Faculty Research Development grant to Erin McClelland. Luke Horner was supported by a MU-WCOM Summer Research Stipend. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)