The gastrointestinal (GI) tract of infant and adult humans is often colonized with Candida sp., most often C. albicans and it is generally believed that in most instances disseminated candidiasis results from systemic spread from that site under conditions of compromise. Little is known of specific immune responses to Candida in the healthy colonized individual, or in the colonized individual who subsequently develops systemic candidiasis under conditions of compromise. The major objective of this research, therefore, is to study the immunologic consequences of long-term colonization with C. albicans using an infant mouse model in which infants become colonized by nursing from mammary glands contaminated with C albicans, and an adult model where mice treated with antibiotics are intubated intragastrically with the fungus. Immune responses to colonization in infants as they mature and in adults as the Candida persists over time, will be studied. Specifically assays will be performed at regular intervals for 1) cellular immunity, detected in vivo by footpad assay and in vitro by lymphocyte stimulation assays, 2) humoral immunity, detected in ELISA assays for secretory and serum antibodies or in plaque assays for antibody-forming cells in spleen cell populations, and 3) the development of a protective response, demonstrable by intravenous challenge. Candida-specific monoclonal IgA will be produced and attempts will be made to determine if it will prevent colonization of the GI tract by Candida. Possible immunoregulatory influences of colonization will be determined by attempting to immunize colonized animals under conditions known to stimulate specific humoral and cellular responses in uncolonized animals. If Candida-specific suppressor cell activity is noted, attempts will be made to identify the source of suppressor activity, e.g., Peyer's patches, and the surface phenotype of the suppressor cell, e.g., Lyt 2. If time permits, using the immune parameters mentioned above, the specific immunologic consequences of antibiotic and cytoreductive drug treatment of colonized and/or immunized mice will be determined.
| Garner, R E; Kuruganti, U; al-Hussaini, L A et al. (1992) Effect of in vivo administration of recombinant murine gamma interferon on in vitro lymphoproliferative responses following immunization with Candida albicans. Infect Immun 60:1927-35 |
| Garner, R E; Kuruganti, U; Czarniecki, C W et al. (1989) In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon. Infect Immun 57:1800-8 |
| Domer, J E (1988) Intragastric colonization of infant mice with Candida albicans induces systemic immunity demonstrable upon challenge as adults. J Infect Dis 157:950-8 |
| Domer, J E; Hector, R F (1987) Enhanced immune responses in mice treated with penicillin-tetracycline or trimethoprim-sulfamethoxazole when colonized intragastrically with Candida albicans. Antimicrob Agents Chemother 31:691-7 |
