Sunday, April 6, 2025
4/6/2025
Induction of Protective Immune Responses Against C. neoformans in Immune Compromised Hosts - Cryptococcus neoformans infections are a significant cause of morbidity and mortality among AIDS patients. Cryptococcal meningoencephalitis is the most common disseminated fungal disease in AIDS patients and is responsible for 15% of AIDS-related deaths globally. Because host immune responses are so vital to the control of cryptococcosis, the overall objective of our laboratory is to determine the mechanism(s) necessary to elicit protective immunity against C. neoformans infections in immune deficient hosts. To this end, studies in our laboratory employ a C. neoformans strain engineered to express interferon (IFN)-, designated H99, as a model system to define protective immune responses against C. neoformans. Published studies by our lab demonstrated that immunization with H99 induces protective immunity against cryptococcosis in mice altogether deficient in B cells, CD4+ T cells, CD8+ T cells, NK cells and neutrophils. Preliminary results provided herein suggest that conventional DC1 cells (cDC1s) are critical for the development of macrophage anti- microbial activity, optimal T cell responses and the induction of protective immunity against cryptococcosis. Taken together, our results lead us to hypothesize that cDC1s are critical for the elicitation of protective vaccine-mediated immune responses against cryptococcosis in CD4+ T cell deficient hosts. The foundation for our hypothesis is supported by a scientifically rigorous set of published and preliminary results that demonstrate the potential impact of strategies that prime cDC1s to elicit protective immunity against cryptococcosis in immune deficient hosts. To test our hypothesis, we propose to define the mechanism(s) by which IFN- primed cDC1s mediate protective anti-Cryptococcus immune responses in immune compromised hosts.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).