Microsporidia are eukaryotic, obligate, intracellular protists that are emerging pathogens in immunocompromised hosts, including AIDS patients and organ transplant recipients. The efficacy of gamma interferon (IFN-gamma) for the treatment of microsporidiosis caused by Encephalitozoon cuniculi was studied by means of adoptive transfer and IFN-gamma administration in SCID mice. While the adoptive transfer of CD4(+) T cells from immunocompetent mice prolonged survival of SCID mice infected perorally with E. cuniculi, survival was not improved by adoptive transfer of CD4(+) T lymphocytes from IFN-gamma-deficient mice. The protective effect of IFN-gamma was confirmed in cytokine therapy experiments in which SCID mice receiving IFN-gamma survived significantly longer than mice receiving mock injections. The administration of serum containing specific antibodies against E. cuniculi was found to prolong the survival of concurrently IFN-gamma-treated SCID mice. The data presented in this study suggest that IFN-gamma is potentially useful as a cytokine therapy for microsporidiosis, especially in CD4(+) T-cell-deficient patients.

Institute of Parasitology and Faculty of Biological Sciences Biology Centre Academy of Sciences of Czech Republic Branisovská 31 370 05 Ceské Budejovice Czech Republic

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Bacchi, C. J., L. M. Weiss, S. Lane, B. Frydman, A. Valasinas, V. Reddy, J. S. Sun, L. J. Marton, I. A. Khan, M. Moretto, N. Yarlett, and M. Wittner. 2002. Novel synthetic polyamines are effective in the treatment of experimental microsporidiosis, an opportunistic AIDS-Associated infection. Antimicrob. Agents Chemother. 46:55-61. PubMed PMC

Braunfuchsova, P., J. Salat, and J. Kopecky. 2002. Comparison of the significance of CD4+ and CD8+ T lymphocytes in the protection of mice against Encephalitozoon cuniculi infection. J. Parasitol. 88:797-799. PubMed

Clemons, K. V., J. E. Lutz, and D. A. Stevens. 2000. Efficacy of recombinant gamma interferon for treatment of systemic cryptococcosis in SCID mice. Antimicrob. Agents Chemother. 45:486-489. PubMed PMC

Didier, E. S., J. A. Maddry, P. J. Brindley, M. E. Stovall, and P. J. Didier. 2005. Therapeutic strategies for human microsporidia infections. Expert Rev. Anti-Infect. Ther. 3:419-434. PubMed

Didier, E. S., and J. A. Shadduck. 1994. IFN-γ and LPS induce murine macrophages to kill Encephalitozoon cuniculi in vitro. J. Eukaryot. Microbiol. 41:43. PubMed

Didier, E. S. 1995. Reactive nitrogen intermediates implicated in the inhibition of Encephalitozoon cuniculi (phylum Microspora) replication in murine peritoneal macrophages. Parasite Immunol. 17:405-412. PubMed

Di Virgilio, F., B. C. Meyer, S. Greenberg, and S. C. Silverstein. 1988. Fc receptor-mediated phagocytosis occurs in macrophages at exceedingly low cytosolic Ca2+ levels. J. Cell Biol. 106:657-666. PubMed PMC

Franzen, C., A. Muller, P. Hartmann, and B. Salzberger. 2005. Cell invasion and intracellular fate of Encephalitozoon cuniculi (Microsporidia). Parasitology 130:285-292. PubMed

Jelinek, J., J. Salat, B. Sak, and J. Kopecky. 2007. Effects of interferon gamma and specific polyclonal antibody on the infection of murine peritoneal macrophages and murine macrophage cell line PMJ2-R with Encephalitozoon cuniculi. Folia Parasitol. 54:172-176. PubMed

Khan, I. A., and M. Moretto. 1999. Role of gamma interferon in cellular immune response against murine Encephalitozoon cuniculi infection. Infect. Immun. 67:1887-1893. PubMed PMC

Khan, I. A., M. Moretto, and L. M. Weiss. 2001. Immune response to Encephalitozoon cuniculi infection. Microbes Infect. 3:401-405. PubMed PMC

Kodjikian, L., J. G. Garweg, M. Nguyen, T. Schaffner, P. Deplazes, and S. Zimmerli. 2005. Intraocular microsporidiosis due to Encephalitozoon cuniculi in a patient with idiopathic CD4+ T lymphocytopenia. Int. J. Med. Microbiol. 294:529-533. PubMed

Kolls, J. K., S. Habetz, M. K. Shean, C. Vazquez, J. A. Brown, D. Lei, P. Schwarzenberger, P. Ye, S. Nelson, W. R. Summer, and J. E. Shellito. 1999. IFN-gamma and CD8+ T cells restore host defenses against Pneumocystis carinii in mice depleted of CD4+ T cells. J. Immunol. 162:2890-2894. PubMed

Koudela, B., J. Lom, J. Vitovec, Z. Kucerova, O. Ditrich, and J. Travnicek. 1994. In vivo efficacy of albendazole against Encephalitozoon cuniculi in SCID mice. J. Eukaryot. Microbiol. 41:49-50. PubMed

Leav, B. A., M. Yoshida, K. Rogers, S. Cohen, N. Godiwala, R. S. Blumberg, and H. Ward. 2005. An early intestinal mucosal source of gamma interferon is associated with resistance to and control of Cryptosporidium parvum infection in mice. Infect. Immun. 73:8425-8428. PubMed PMC

Molina, J. M., M. Tourneur, C. Sarfati, S. Chevret, A. de Gouvello, J. G. Gobert, S. Balkan, and F. Derouin. 2002. Fumagillin treatment of intestinal microsporidiosis. N. Engl. J. Med. 346:1963-1969. PubMed

Orenstein, J. M., H. P. Gaetz, A. T. Yachnis, S. S. Frankel, R. B. Mertens, and E. S. Didier. 1997. Disseminated microsporidiosis in AIDS: are any organs spared? AIDS 11:385-386. PubMed

Reljic, R. 2007. IFN-gamma therapy of tuberculosis and related infections. J. Interferon Cytokine Res. 27:353-364. PubMed

Sak, B., J. Salat, H. Horka, K. Sakova, and O. Ditrich. 2006. Antibodies enhance the protective effect of CD4+ T lymphocytes in SCID mice perorally infected with Encephalitozoon cuniculi. Parasite Immunol. 28:95-99. PubMed

Salat, J., B. Sak, T. Le, and J. Kopecky. 2004. Susceptibility of IFN-gamma or IL-12 knockout and SCID mice to infection with two microsporidian species, Encephalitozoon cuniculi and E. intestinalis. Folia Parasitol. 51:275-282. PubMed

Salat, J., H. Horka, B. Sak, and J. Kopecky. 2006. Pure CD4+ T lymphocytes fail to protect perorally infected SCID mice from lethal microsporidiosis caused by Encephalitozoon cuniculi. Parasite Res. 99:682-686. PubMed

Southern, T. R., C. E. Jolly, M. E. Lester, and. R. Hayman. 2006. Identification of a microsporidia protein potentially involved in spore adherence to host cells. J. Eukaryot. Microbiol. 53:S68-S69. PubMed

Tremoulet, A. H., M. L. Avila-Aguero, M. M. Paris, A. Canas-Coto, R. Ulloa-Gutierrez, and I. Faingezicht. 2004. Albendazole therapy for microsporidium diarrhea in immunocompetent Costa Rican children. Pediatr. Infect. Dis. 23:915-918. PubMed

Wang, X., H. Kang, T. Kikuchi, and Y. Suzuki. 2004. Gamma interferon production, but not perforin-mediated cytolytic activity, of T cells is required for prevention of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease. Infect. Immun. 72:4432-4438. PubMed PMC

Weber, R., R. T. Bryan, D. A. Schwartz, and R. L. Owen. 1994. Human microsporidial infections. Clin. Microbiol. Rev. 7:426-461. PubMed PMC

Wiwanitkit, V. 2006. Intestinal parasite infestation in HIV-infected patients. Curr. HIV Res. 4:87-96. PubMed

Zhang, H., H. Huang, A. Cali, P. M. Takvorian, X. C. Feng, G. Zhou, and L. M. Weiss. 2005. Investigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis. Folia Parasitol. 52:182-192. PubMed PMC

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