Most cited article - PubMed ID 12197135
Comparison of the significance of CD4+ and CD8+ T lymphocytes in the protection of mice against Encephalitozoon cuniculi infection
Microsporidia are pathogenic organism related to fungi. They cause infections in a wide variety of mammals as well as in avian, amphibian, and reptilian hosts. Many microsporidia species play an important role in the development of serious diseases that have significant implications in human and veterinary medicine. While microsporidia were originally considered to be opportunistic pathogens in humans, it is now understood that infections also occur in immune competent humans. Encephalitozoon cuniculi, Encephalitozoon intestinalis, and Enterocytozoon bieneusi are primarily mammalian pathogens. However, many other species of microsporidia that have some other primary host that is not a mammal have been reported to cause sporadic mammalian infections. Experimental models and observations in natural infections have demonstrated that microsporidia can cause a latent infection in mammalian hosts. This chapter reviews the published studies on mammalian microsporidiosis and the data on chronic infections due to these enigmatic pathogens.
- Keywords
- Epidemiology, Infection, Latency, Mammals, Microsporidia, Recurrent infection, Transmission,
- MeSH
- Enterocytozoon * MeSH
- Feces microbiology MeSH
- Humans MeSH
- Microsporidia * genetics MeSH
- Persistent Infection MeSH
- Mammals MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Encephalitozoonosis is a common infectious disease widely spread among rabbits. Encephalitozoon cuniculi, is considered as a zoonotic and emerging pathogen capable of infecting both immunocompetent and immunocompromised hosts. The aim of the study was to describe in detail the spread of the E. cuniculi in a rabbit organism after experimental infection and the host humoral and cellular immune response including cytokine production. For that purpose, healthy immunocompetent rabbits were infected orally in order to simulate the natural route of infection and euthanised at 2, 4, 6 and 8-weeks post-infection. Dissemination of E. cuniculi in the body of the rabbit was more rapid than previously reported. As early as 2 weeks post-infection, E. cuniculi was detected using immunohistochemistry not only in the intestine, mesenteric lymph nodes, spleen, liver, kidneys, lungs and heart, but also in nervous tissues, especially in medulla oblongata, cerebellum, and leptomeninges. Based on flow cytometry, no conspicuous changes in lymphocyte subpopulations were detected in the examined lymphoid organs of infected rabbits. Cell-mediated immunity was characterized by ability of both CD4+ and CD8+ T cells to proliferate after stimulation with specific antigens. Th1 polarization of immune response with a predominance of IFN-γ expression was detected in spleen, mesenteric lymph nodes and Peyer's patches. The increased expression of IL-4 and IL-10 mRNA in mixed samples from the small intestine is indicative of balanced control of IFN-γ, which prevents tissue damage. On the other hand, it can enable E. cuniculi to survive and persist in the host organism in a balanced host-parasite relationship. The Th17 immunity lineage seems to play only a minor role in E. cuniculi infection in rabbits.
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.
- MeSH
- CD4-Positive T-Lymphocytes immunology MeSH
- Encephalitozoon cuniculi immunology MeSH
- Encephalitozoonosis immunology mortality parasitology therapy MeSH
- Immunotherapy MeSH
- Interferon-gamma administration & dosage genetics therapeutic use MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Antibodies, Monoclonal immunology therapeutic use MeSH
- Mice, Inbred BALB C MeSH
- Mice, Knockout MeSH
- Mice, SCID MeSH
- Mice MeSH
- Adoptive Transfer MeSH
- Antibody Specificity * MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Interferon-gamma MeSH
- Antibodies, Monoclonal MeSH
The role of CD4+ and CD8+ T lymphocytes in the protection against intraperitoneally (i.p.) or perorally (p.o.) acquired Encephalitozoon cuniculi (Levaditi et al., C R Soc Biol Paris 89:984-986, 1923) infection was studied by means of reconstitution of severe combined immunodeficiency (SCID) mice with well-defined populations of naive CD8+ or CD4+ T lymphocytes. Adoptive transfer of pure CD8+ T lymphocyte subpopulation protects SCID mice against a lethal microsporidiosis caused by E. cuniculi. The protective effect of CD8+ T lymphocytes is manifested in both i.p. and p.o. infection. On the contrary, the host defense against peroral infection does not require CD8+ T cells. The protective role is not mediated by CD4+ T lymphocytes only. SCID mice reconstitution with pure CD4+ T cell subpopulation led to prolonged survival of perorally infected mice. However, these mice died due to lethal encephalitozoonosis caused by i.p. infection.
- MeSH
- CD4-Positive T-Lymphocytes immunology MeSH
- CD8-Positive T-Lymphocytes immunology MeSH
- Encephalitozoon cuniculi immunology MeSH
- Encephalitozoonosis immunology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Adoptive Transfer MeSH
- Severe Combined Immunodeficiency immunology MeSH
- Mouth MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
