EXPERIMENTAL MICROSPORIDIOSIS IN IMMUNOCOMPETENT AND IMMUNODEFICIENT MICE AND MONKEYS

Microsporidia cause opportunistic infections in AIDS patients and comm only infect laboratory animals, as well. Euthymic C57B1/6 mice experim entally infected with intraperitoneal injections of 1x10(6) Encephalit ozoon cuniculi Levaditi, Nicolau et Schoen, 1923, Encephalitozoon hell em Didier et al., 1991, or Nosema corneum Shadduck et al., 1990 displa yed no clinical signs of disease. Athymic mice, however, developed asc ites and died 8-16 days after inoculation with N. corneum, 21-25 days after inoculation with E. cuniculi, and 34-37 days after inoculation w ith E. hellem. All athymic mice displayed hepatomegaly, dilated intest ine and accumulation of ascites fluid. Granulomatous lesions were prim arily located in the liver, lung, pancreas, spleen, and on serosal sur faces of abdominal organs. The murine microsporidiosis model also was used to examine immune response that inhibit microsporidia growth in v itro. Recombinant murine interferon-gamma (mIFN-gamma, 100 u/ml) alone or in combination with lipopolysaccharide (LPS; 10 ng/ml) could activ ate thioglycollate-induced peritoneal murine macrophages to destroy E. cuniculi. The production of the nitrogen intermediate, NO2-, correlat ed with parasite destruction. Inhibition of NO2- generation by additio n of the L-arginine analogue, N(G)-monomethyl L-arginine (NMMA), inhib ited microsporidia killing, as well. Since microsporidiosis is becomin g an important opportunistic infection in AIDS patients, a microsporid iosis model is being developed using SIV/DeltaB670-infected rhesus mac aque monkeys (Macaca mulatta). SIV-infected immunocompetent monkeys gi ven E. cuniculi or E. hellem per os developed specific antibodies, and microsporidia could be detected sporadically by calcofluor or antibod y fluorescence staining of stool and urine sediment smears. As immunod eficiency progressed, monkeys developed diarrhoea, cachexia, and anore xia, and organisms were detected in urine and stool with greater frequ ency. Immunodeficient SIV-infected monkeys died approximately 27 days after receiving E. hellem by intravenous inoculation, and approximatel y 110 days after receiving E. hellem per os. Lesions typical for SIV-i nfection were observed in both groups of monkeys and microsporidia wer e detected in kidney and liver of the intravenously-injected monkeys. The murine microsporidiosis model provides an efficient means for stud ying protective immune responses to microsporidiosis, and may prove us eful for screening immunological and chemotherapeutic agents. The path ogenesis of Encephalitozoon microsporidiosis in SIV-infected monkeys a ppears to parallel encephatilozoonosis in AIDS patients, suggesting th at simian microsporidiosis may provide a useful model for evaluating d iagnostic methods and therapeutic strategies during various stages of progressing immunodeficiency.