The Role of Sex Steroid Hormones in CD4+ T Cell-mediated Immune Responses to Tuberculosis

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Abstract A large body of evidence indicates that males are more likely to develop active pulmonary tuberculosis (TB) than females. However, research studies on this theme have been primarily focused on characterizing the epidemiology of TB in a sex-specific manner with little to no exploration of the biological mechanisms driving sex differences in TB outcomes. For this reason, in 2019, I have initiated a research project as part of a career development award (K43TW011426) to investigate the role of sex steroid hormones, namely testosterone and estradiol, on immune responses to tuberculosis. During the beginning of this project, I was directly impacted by unforeseen challenges, including COVID-19 pandemic and prolonged crisis in Mali, which led to an inability to travel to the US for experiential training and procure reagents and supplies from international vendors at regular costs. I am now proposing supplemental activities, including laboratory training and experiments to be conducted both at the Johns Hopkins University and the University Clinical Research Center (UCRC) in Mali. The activities include multiparameter flow cytometry and co-treatment of immune cells with mycobacterium antigens and sex steroid hormones ex vivo prior acquisition by flow cytometry. These activities were carefully designed to directly respond to the urgent need of finishing the experiments proposed in the parent award and increase the likelihood of success in applying for an R-type application next year.