Cryptococcosis is a mycotic disease that is acquired by inhalation of the ubiquitous yeast-like organism, Cryptococcus neoformans. The primary pulmonary disease can range from mild to severe depending on the host's immunological status. The goal is to identify the mechanisms by which the anticryptococcal responses are down- regulated.
The specific aims are: 1) to assess the role of IL-10 and IL- 4 in down-regulation of the anticryptococcal CMI response in mice infected with C. neoformans isolate NU-2 or 184A; 2) to examine the temporal profile of TGF-beta and TNFalpha and determine if blocking the activity of either or both of these cytokines would alter the anticryptococcal CMI response; 3) to determine if leukocyte surface markers such as B7-1, B7-2, major histocompatibility complex (MHC) class II antigens (1-A and I-E) on antigen presenting cells and CD28 and CTLA-4 on CD4plus and CD8plus T lymphocytes are modulated and examine the potential for the changes to contribute to the deviation in the anticryptococcal CMI response in NU-2-infected mice; 4) to examine the role of Fas/FasL-mediated apoptosis in the regulation of the anticryptococcal CMI response in the NU-2 infected mice; and 5) to apply differential display polymerase chain reaction (DD-PCR) technology to establish differences in mRNAs inducted by an infection with NU-2 (modulated CMI response) compared to mRNAs induced by an infection with 184A (prolonged protective CMI response) in the mouse model.
