Dissemination of <i>Encephalitozoon intestinalis,</i> a causative agent of human microsporidiosis, in IFN‐γ receptor knockout mice

Fakhry, Youssef El; Achbarou, Abderrahim; Franetich, Jean‐François; Mazier, Dominique

doi:10.1046/j.1365-3024.2001.00351.x

Cited by 12 publications

(9 citation statements)

References 32 publications

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“…Se ha reportado que la inmunidad mediada por linfocitos T (LT) juega un papel importante en la defensa de la infección con microsporidios; algunos autores señalan que la respuesta inmune del hospedero contra estos parásitos es del tipo Th1 con producción de IL-2 e INFγ (8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

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Efecto de la ciclosporina A en ratones C57BL/6 infectados con Encephalitozoon intestinalis.

et al. 2006

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Introducción. Encephalitozoon intestinalis es un microsporidio parásito del intestino, que puede diseminarse en pacientes inmunocomprometidos. Existen referencias de modelos animales inmunosuprimidos para el estudio de la microsporidiosis utilizando fármacos que producen supresión total de la respuesta inmune; sin embargo, no se han estudiado los efectos de inmunosupresores con acción selectiva sobre los componentes de esta respuesta. Objetivo. Evaluar el efecto de la inmunosupresión con ciclosporina A (CsA) en ratones C57BL/ 6 infectados con E. intestinalis. Materiales y métodos. Se utilizaron 80 ratones C57BL/6 distribuidos en cuatro grupos: infectados, inmunosuprimidos e infectados, inmunosuprimidos no infectados y controles. La inmunosupresión con CsA (50 mg/kg) se realizó vía intraperitoneal durante todo el estudio. En la semanas 2, 3, 4 y 6 posteriores a la infección se obtuvo sangre para determinar los anticuerpos, y materia fecal para evaluar la cinética de excreción de esporas. Además, se extrajeron varios órganos para estudiar la histopatología y observar la posible diseminación del parásito. Resultados. La producción de anticuerpos IgG fue mayor en los ratones inmunocompetentes infectados que en los inmunosuprimidos infectados con E. intestinalis. No se encontró el parásito en órganos diferentes al intestino delgado en los dos grupos infectados. Sin embargo, la excreción de esporas, tanto en heces como en líquido duodenal, fue mayor en el grupo inmunosuprimido infectado. Conclusión. La CsA en el modelo en ratón no indujo la diseminación de E. intestinalis ni la exacerbación de la enfermedad, pero contribuyó al aumento en la cinética de excreción de esporas y la disminución de la producción de anticuerpos IgG en los ratones inmunosuprimidos infectados.Palabras clave: microsporidios no clasificados, microsporidiosis, formación de anticuerpos, inmunosupresión, ciclosporina. Cyclosporine A effect in mice C57BL/6 infected with Encephalitozoon intestinalis.Introduction. Encephalitozoon intestinalis, a parasite belonging to the phylum Microsporidia, is causes gastrointestinal infections in the immunocompromised host. A suitable pharmacologically immunosuppressed animal model for the study of natural E. intestinalis infection, which can establish the immune components that respond to this parasite, is lacking. Objective. To evaluate the effect of immunosuuppression with Cyclosporine A (CsA) in C57BL/ 6 mice on experimental infection with E.intestinalis infection. Materials and methods. Eighty C57BL/6 mice were distributed in four treatment groups: Control, CsA-immunosuppressed mice without infection, immunocompetent and immunossuppressed mice infected with E. intestinalis. Mice were immunosuppressed with a weekly dose of 50mg/ Kg body weight of CsA, during the course of the study. Five mice from each group were sacrificed 2, 3, 4 and 6 weeks post-infection, to obtain blood for antibody testing and stool samples were analyzed to assess excretion of spores.

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Efecto de la ciclosporina A en ratones C57BL/6 infectados con Encephalitozoon intestinalis.

et al. 2006

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“…Subsequent studies confirmed the suppressive effect of IFNγ on E. cuniculi growth as well as on E. intestinalis using murine peritoneal macrophages [31] , [32] , the murine enterocyte cell line CMT-93 and human enterocyte cell line Caco-2 [33] as well as primary human monocyte-derived macrophages [34] . Furthermore, IFNγ-deficient mice are susceptible to E. cuniculi and E. intestinalis infection [32] , [35] , [36] , [37] . It is characteristic of the IRG resistance system that it is efficient in non-myeloid cells such as fibroblasts [1] , [4] , [38] .…”

Section: Resultsmentioning

confidence: 99%

Identification of the Microsporidian Encephalitozoon cuniculi as a New Target of the IFNγ-Inducible IRG Resistance System

et al. 2014

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The IRG system of IFNγ-inducible GTPases constitutes a powerful resistance mechanism in mice against Toxoplasma gondii and two Chlamydia strains but not against many other bacteria and protozoa. Why only T. gondii and Chlamydia? We hypothesized that unusual features of the entry mechanisms and intracellular replicative niches of these two organisms, neither of which resembles a phagosome, might hint at a common principle. We examined another unicellular parasitic organism of mammals, member of an early-diverging group of Fungi, that bypasses the phagocytic mechanism when it enters the host cell: the microsporidian Encephalitozoon cuniculi. Consistent with the known susceptibility of IFNγ-deficient mice to E. cuniculi infection, we found that IFNγ treatment suppresses meront development and spore formation in mouse fibroblasts in vitro, and that this effect is mediated by IRG proteins. The process resembles that previously described in T. gondii and Chlamydia resistance. Effector (GKS subfamily) IRG proteins accumulate at the parasitophorous vacuole of E. cuniculi and the meronts are eliminated. The suppression of E. cuniculi growth by IFNγ is completely reversed in cells lacking regulatory (GMS subfamily) IRG proteins, cells that effectively lack all IRG function. In addition IFNγ-induced cells infected with E. cuniculi die by necrosis as previously shown for IFNγ-induced cells resisting T. gondii infection. Thus the IRG resistance system provides cell-autonomous immunity to specific parasites from three kingdoms of life: protozoa, bacteria and fungi. The phylogenetic divergence of the three organisms whose vacuoles are now known to be involved in IRG-mediated immunity and the non-phagosomal character of the vacuoles themselves strongly suggests that the IRG system is triggered not by the presence of specific parasite components but rather by absence of specific host components on the vacuolar membrane.

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“…IFN‐γ plays a major part in the immunological control of E. intestinalis and helps to prevent dissemination of the infection to other organs (9–11) but the role of the cytokine in inducing intestinal epithelium to inactivate the parasite has not been investigated. Findings in the present study indicate that IFN‐γ‐primed enterocytes may play a vital role in eliminating the parasite.…”

Section: Discussionmentioning

confidence: 99%

“…IFN‐γ −/– or IFN‐γR −/– mice fail to control parasite reproduction effectively indicating the importance of IFN‐γ activity in control of infection (9,10). IFN‐γ is also required to prevent dissemination of E. intestinalis from the gut epithelium to other organs but how this is achieved is not known (11).…”

Section: Introductionmentioning

confidence: 99%

Interferon‐γ‐mediated activation of enterocytes in immunological control of Encephalitozoon intestinalis infection

Choudhry

Korbel

Zaalouk

et al. 2008

Parasite Immunology

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The microsporidian Encephalitozoon intestinalis develops within intestinal epithelial cells (enterocytes) and is an important opportunistic diarrhoeal pathogen associated with AIDS. Little is known about the protective immune response against the parasite although in mice IFN-gamma is involved and is required to prevent dissemination of the infection to other organs. The present study was designed to establish a suitable short-term in vitro culture technique for E. intestinalis that would enable studies of the role of cytokines such as IFN-gamma in the effector phase of immunity. Encephalitozoon intestinalis reproduced considerably better in the murine enterocyte cell line CMT-93 than in the three human enterocyte cell lines Caco-2, HT29 and HCT-8. Treatment of CMT-93 cells with IFN-gamma significantly reduced parasite reproduction in a dose- and time-dependent manner. IFN-gamma also inhibited development of the parasite in Caco-2 cells. Neither production of NO nor Fe deprivation appeared to be involved in IFN-gamma-mediated parasite killing. However studies suggested that tryptophan catabolism by indoleamine 2,3-dioxygenase played an important part in inactivation of E. intestinalis.

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Dissemination of Encephalitozoon intestinalis, a causative agent of human microsporidiosis, in IFN‐γ receptor knockout mice

Cited by 12 publications

References 32 publications

Efecto de la ciclosporina A en ratones C57BL/6 infectados con Encephalitozoon intestinalis.

Efecto de la ciclosporina A en ratones C57BL/6 infectados con Encephalitozoon intestinalis.

Identification of the Microsporidian Encephalitozoon cuniculi as a New Target of the IFNγ-Inducible IRG Resistance System

Interferon‐γ‐mediated activation of enterocytes in immunological control of Encephalitozoon intestinalis infection

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