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The Role of Host Gender in the Pathogenesis of Cryptococcus neoformans Infections Erin E. McClelland1,5*, Letizia M. Hobbs1,6, Johanna Rivera2, Arturo Casadevall2, Wayne K. Potts3, Jennifer M. Smith1, Jeramia J. Ory1,4 1 The Commonwealth Medical College, Department of Basic Sciences, Scranton, Pennsylvania, United States of America, 2 Albert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, New York, United States of America, 3 University of Utah, Department of Biology, Salt Lake City, Utah, United States of America, 4 King’s College, Department of Biology, Wilkes-Barre, Pennsylvania, United States of America, 5 Middle Tennessee State University, Department of Biology, Murfreesboro, Tennessee, United States of America, 6 Musculoskeletal Transplant Foundation, Microbiology Laboratory, Jessup, Pennsylvania, United States of America Abstract Cryptococcus neoformans (Cn) is a pathogenic yeast and the cause of cryptococcal meningitis. Prevalence of disease between males and females is skewed, with males having an increased incidence of disease. Based on the reported gender susceptibility differences to Cn in the literature, we used clinical isolates from Botswanan HIV-infected patients to test the hypothesis that different gender environments exerted different selective pressures on Cn. When we examined this data set, we found that men had significantly higher risk of death despite having significantly higher CD4+ T lymphocyte counts upon admittance to the hospital. These observations suggested that Cn strains are uniquely adapted to different host gender environments and that the male immune response may be less efficient in controlling Cn infection. To discriminate between these possibilities, we tested whether there were phenotypic differences between strains isolated from males and females and whether there was an interaction between Cn and the host immune respon
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