The overall objective of this proposal is to study the host/pathogen interaction at mucosal surfaces and to? develop prevention strategies that maximize protective mucosal immune responses to Cryptosporidium? parvum (C. parvuni). We will develop and maintain a murine model for murine acquired immunodeficiency? syndrome (MAIDS) which will be used to study the pathogenesis of C. parvum; a potential pathogen? commonly associated with AIDS patients. To develop the MAIDS model, C57BL/6 female mice will be? immunosuppressed by inoculation with LP-BM5; then challenged with C. parvum 3 months post-infection.? Studies of experimentally induced cryptosporidiosis using this model, will serve as a relevant tool for? evaluating various therapies for prevention of this opportunistic disease specifically in AIDS patients. Our? previous studies have confirmed that mice infected with LP-BM5, develop persistent experimental? cryptosporidiosis with high numbers of Oocysts shedding in the feces. Since the spread of AIDS is global and? frequently associated with opportunistic infections including cryptosporidiosis, it is critical to control these? diseases in AIDS patients to alleviate human suffering to minimize both soscial and economic impact on? society. Our long range goal will be to develop effective prophylactic regimens for the control of? Cryptosporidium infection, especially through nutritional, immunotherapeutic or chemotherapeutic? interventions. As yet, no effective treatment for cryptosporidiosis has been reported. We will achieve the? following specific aims during these studies: (a) elucidate the role of cellular gut immunity to C. parvum in? this MAIDS model by determining the roles and phenotypic frequencies of intestinal intraepithelial (lEL's)? and lamina propria (LPL) subpopulations (CD4+, CD8+, IgA+, IgG+ and IgM+) and cytokine (TNF-a, INF-y,? IL-2, 4, 5 and 10) production post C. parvum challenge, (b) evalute the efficacy of Lactobacillus reuteri and? acidophillus as probiotics for the control of cryptosporidiosis and (c) evalute the efficacy of probiotics and? vaccines administered simultaneously for the control of cryptosporidiosis. Results obtained from these studies? will be relevant in the development of new therapies for the control of cryptosporidiosis and other? opportunistic diseases in immuncompromised individuals especially AIDS subjects.
