Nejvíce citovaný článek - PubMed ID 16441507
Antibodies enhance the protective effect of CD4+ T lymphocytes in SCID mice perorally infected with Encephalitozoon cuniculi
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.
- Klíčová slova
- Epidemiology, Infection, Latency, Mammals, Microsporidia, Recurrent infection, Transmission,
- MeSH
- Enterocytozoon * MeSH
- feces mikrobiologie MeSH
- lidé MeSH
- Microsporidia * genetika MeSH
- perzistentní infekce MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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.
- MeSH
- buněčná imunita * MeSH
- Encephalitozoon cuniculi fyziologie MeSH
- encephalitozoonóza imunologie parazitologie veterinární MeSH
- humorální imunita * MeSH
- imunokompetence MeSH
- králíci * MeSH
- zvířata MeSH
- Check Tag
- králíci * MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Microsporidia are obligate intracellular parasites causing severe infections with lethal outcome in immunocompromised hosts. However, these pathogens are more frequently reported as latent infections in immunocompetent individuals and raises questions about the potential risk of reactivation following induced immunosuppression. AIMS: To evaluate the possibility latent microsporidiosis, efficacy or albendazole, and reactivation, the authors monitored the course of E. cuniculi infection in immunocompetent BALB/c mice and immunodeficient SCID mice using molecular methods. METHODS: Mice were per orally infected with 10(7) spores of E. cuniculi. Selected groups were treated with albendazole, re-infected or chemically immunosuppressed by dexamethasone. The presence of microsporidia in the host's organs and feces were determined using PCR methods. Changes in numbers of lymphocytes in blood and in spleen after induction of immunosuppression were confirmed using flow cytometry analysis. RESULTS: Whereas E. cuniculi caused lethal microsporidiosis in SCID mice, the infection in BABL/c mice remained asymptomatic despite parasite dissemination into many organs during the acute infection phase. Albendazole treatment led to microsporidia elimination from organs in BALB/c mice. In SCID mice, however, only a temporary reduction in number of affected organs was observed and infection re-established post-treatment. Dexamethasone treatment resulted in a chronic microsporidia infection disseminating into most organs in BALB/c mice. Although the presence of E. cuniculi in organs of albendazole- treated mice was undetectable by PCR, it was striking that infection was reactivated by immunosuppression treatment. CONCLUSION: Our results demonstrated that microsporidia can successfully survive in organs of immunocompetent hosts and are able to reactivate from undetectable levels and spread within these hosts after induction of immunosuppression. These findings stress the danger of latent microsporidiosis as a life-threatening risk factor especially for individuals undergoing chemotherapy and in transplant recipients of organs originating from infected donors.
- MeSH
- albendazol terapeutické užití MeSH
- Cercopithecus aethiops MeSH
- dexamethason MeSH
- Encephalitozoon cuniculi * MeSH
- encephalitozoonóza farmakoterapie imunologie MeSH
- feces mikrobiologie MeSH
- modely nemocí na zvířatech * MeSH
- myši inbrední BALB C MeSH
- myši SCID MeSH
- myši MeSH
- počet lymfocytů MeSH
- polymerázová řetězová reakce MeSH
- průtoková cytometrie MeSH
- Vero buňky MeSH
- vnitřnosti mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- albendazol MeSH
- dexamethason MeSH
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-pozitivní T-lymfocyty imunologie MeSH
- Encephalitozoon cuniculi imunologie MeSH
- encephalitozoonóza imunologie mortalita parazitologie terapie MeSH
- imunoterapie MeSH
- interferon gama aplikace a dávkování genetika terapeutické užití MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- monoklonální protilátky imunologie terapeutické užití MeSH
- myši inbrední BALB C MeSH
- myši knockoutované MeSH
- myši SCID MeSH
- myši MeSH
- převzatá imunita MeSH
- specificita protilátek * MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interferon gama MeSH
- monoklonální protilátky 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-pozitivní T-lymfocyty imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- Encephalitozoon cuniculi imunologie MeSH
- encephalitozoonóza imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- převzatá imunita MeSH
- těžká kombinovaná imunodeficience imunologie MeSH
- ústa MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH