MURINE AIDS MODEL: C PARVUM PROBIOTICS, OPPORTUNISTIC INFEC: MAIDS: TCR GENE:

本提案的总体目标是研究

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 Cryptosporidiumum parvum (C parvum). We will develop and maintain a murine model for murine acquired immunodeficiency syndrome (MAIDS) which will be used to study the pathogenesis of C parmm; a potential pathogen commonly associated with AIDS. To develop the MAIDS model, C57BI_16 female mice win be immunosuppressed by inoculation with LP-BM5; then challenged with C parvum 3 months post LP-BM5 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 as our previous studies have confirmed that mice infected with LP-BM5, develop persistent experimental cryptosporidiosis with high numbers of oocysts shed in the feces. Since the spread of AIDS is global and frequently assoc iated with opportunistic infections including cryptosporidiosis, it is critical to control AIDS-related o0portunistic diseases to alleviate human suffering in order to minimize both social 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: elucidate the role of cellular gut immunity to C parvum in this MAIDS model by determining the roles and phenotypic frequencies of intestinal (1) intraepithelial (EEL's) and (2) lamina propria (LPL) subpopulations (CD4', CD8, IgA, IgG' and IgM') and cytokine (TNF-a , IFN-y, IL-1, IL-2, 4, 5 and 10) production post C parvum challenge. (3) evaluate the efficacy of Lactobacillus reuteri and L. acidophilus as probiotics for the control of cryptosporidiosis and (4) evaluate the efficacy of probiotics and (5) vavvines 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.