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.