RESUMO
Microsporidia are intracellular pathogens that cause severe disease in immunocompromised humans and animals. We recently demonstrated that XID mice are more susceptible to Encephalitozoon cuniculi infection by intraperitoneal route, evidencing the role of B-1 cells in resistance against infection. The present study investigated the resistance and susceptibility against E. cuniculi oral infection, including the role of B-1 cells. BALB/c and BALB/c XID (B-1 cells deficient) mice were orally infected with E. cuniculi spores. No clinical symptoms were observed in infected animals; histopathology showed lymphoplasmocytic enteritis with degeneration of the apexes of the villi in all infected groups. Higher parasite burden was observed in infected BALB/c XID mice. In the spleen and peritoneum, all infected mice showed a decrease of lymphocytes, including CD8+ T cells, mostly in infected BALB/c XID mice. Adoptive transfer of B-1 cells (XID + B-1) was associated with a lower parasite burden. Pro-inflammatory cytokines (IFN-γ, TNF-α and IL-6) increased mostly in infected XID + B1 mice. Together, the present results showed that BALB/c XID mice infected by the oral route were more susceptible to encephalitozoonosis than BALB/c mice, demonstrating the B-1 cells importance in the control of the immune response against oral E. cuniculi infection.
Assuntos
Subpopulações de Linfócitos B/fisiologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/sangue , Encephalitozoon cuniculi/fisiologia , Encefalitozoonose/imunologia , Regulação para Cima/imunologia , Transferência Adotiva , Animais , Subpopulações de Linfócitos B/imunologia , Citocinas/imunologia , Encefalitozoonose/microbiologia , Encefalitozoonose/patologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/imunologia , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/microbiologiaRESUMO
Encephalitozoon cuniculi is an opportunist intracellular pathogen of mammals. The adaptive immune response is essential to eliminate E. cuniculi, but evidence is mounting that the response initiated by the innate immune response may ultimately define whether or not the parasite can survive. B-1 cells may act as antigen-presenting cells or differentiate into phagocytes, playing different roles in many infection models. However, the role of these cells in the dynamics of Encephalitozoon sp. infections is still unknown. To investigate the role of B-1 cells in E. cuniculi infection, BALB/c and BALB/c XID (B-1 cells deficient) mice were infected with E. cuniculi spores. Cytometric analyses of peritoneal cells showed that B-1 cells and macrophages increased significantly in infected BALB/c mice compared to uninfected controls. Despite the increase in the number of CD4+ and CD8+ lymphocytes in XID mice, these animals were more susceptible to infection as evidenced histologically with more prominent inflammatory lesions and parasite burden. Pro-inflammatory cytokines increased in both infected BALB/c and BALB/c XID mice. To confirm B-1 cells role in encephalitozoonosis, we adoptively transferred B-1 cells to BALB/c XID mice and this group showed few symptoms and microscopic lesions, associated with an increased in cytokines. Together, these results suggest that B-1 cells may increase the resistance of BALB/c mice to encephalitozoonosis, evidencing for the first time the important role of B-1 lymphocytes in the control of microsporidia infection.
Assuntos
Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Suscetibilidade a Doenças , Encefalitozoonose/imunologia , Encefalitozoonose/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Encephalitozoon cuniculi/imunologia , Encefalitozoonose/microbiologia , Encefalitozoonose/patologia , Feminino , Contagem de Linfócitos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
Microsporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNγ, CD4+, and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells (DC) play a key role at eliciting anti-microsporidial immunity. We investigated the in vitro response of DC and DC precursors/progenitors to infection with Encephalitozoon intestinalis (Ei), a common agent of human microsporidosis. Ei-exposed DC cultures up-regulated the surface expression of MHC class II and the costimulatory molecules CD86 and CD40, only when high loads of spores were used. A vigorous secretion of IL-6 but not of IL-1ß or IL-12p70 was also observed in these cultures. Ei-exposed DC cultures consisted of immature infected and mature bystander DC, as assessed by MHC class II and costimulatory molecules expression, suggesting that intracellular Ei spores deliver inhibitory signals in DC. Moreover, Ei selectively inhibited the secretion of IL-12p70 in LPS-stimulated DC. Whereas Ei-exposed DC promoted allogeneic naïve T cell proliferation and IL-2 and IFNγ secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNγ secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development toward cells phenotypically or functionally compatible with myeloid-derived suppressor cells. Neutralization experiments demonstrated that this inhibitory effect is IL-6-dependent. Altogether this investigation reveals a novel potential mechanism of immune escape of microsporidian parasites through the modulation of DC differentiation and maturation.
Assuntos
Células Dendríticas/citologia , Células Dendríticas/imunologia , Encephalitozoon/imunologia , Encefalitozoonose/imunologia , Evasão da Resposta Imune/imunologia , Interleucina-6/imunologia , Animais , Antígeno B7-2/biossíntese , Linfócitos T CD4-Positivos/imunologia , Antígenos CD40/biossíntese , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Células Cultivadas , Encefalitozoonose/microbiologia , Interferon gama/imunologia , Interferon gama/metabolismo , Subunidade p35 da Interleucina-12/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Esporos Bacterianos/imunologiaRESUMO
Microsporidioses are considered emerging and opportunistic infections in immunocompromised individuals worldwide. The purpose of this study was to identify the species of intestinal microsporidia in patients with HIV-AIDS from the Servicio Autónomo Hospital Universitario de Maracaibo, Venezuela (SAHUM). Fecal samples were collected from 50 patients with confirmed diagnosis of HIV, during the years 2007 and 2008; the CD4 values were obtained from 42 patients. The samples were analyzed by separate PCRs to identify Encephalitozoon intestinalis and Enterocytozoon bieneusi. Microsporidia species showed a 36% prevalence: ten patients had Encephalitozoon intestinalis, four Enterocytozoon bieneusi and four both species. An inverse and statistically significant relationship between the CD4 count and the presence of microsporidia in the fecal sample was also found. It is remarkable the high prevalence of microsporidia species observed in the HIV patients studied, with a predominance of E. intestinalis.
Assuntos
Diarreia/epidemiologia , Encephalitozoon/isolamento & purificação , Encefalitozoonose/epidemiologia , Enterocytozoon/isolamento & purificação , Fezes/microbiologia , Infecções por HIV/epidemiologia , Microsporidiose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Doenças Assintomáticas , Contagem de Linfócito CD4 , Coinfecção , Comorbidade , DNA Fúngico/análise , Diarreia/microbiologia , Encefalitozoonose/microbiologia , Feminino , Infecções por HIV/imunologia , Síndrome de Emaciação por Infecção pelo HIV/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Microsporidiose/microbiologia , Pessoa de Meia-Idade , Prevalência , Venezuela/epidemiologia , Adulto JovemRESUMO
Los microsporidios pueden provocar infecciones emergentes y oportunistas en individuos inmunocomprometidos de todo el mundo. Se realizó éste estudio para identificar las especies de microsporidios intestinales presentes en pacientes con VIH-SIDA del Servicio Autónomo Hospital Universitario de Maracaibo (SAHUM). Se recolectaron 50 muestras fecales de individuos con diagnóstico confirmado de VIH durante los años 2007-2008; se obtuvieron las cifras de CD4 de solo 42 pacientes. Las muestras se analizaron mediante PCR separadas para la identificación de Encephalitozoon intestinalis y Enterocytozoon bieneusi. Las especies de microsporidios presentaron un 36% de prevalencia, 10 pacientes presentaron Encephalitozoon intestinalis, 4 Enterocytozoon bieneusi y 4 ambas especies. Se determinó una relación inversamente proporcional y estadísticamente significativa entre el contaje de CD4 y la presencia de microsporidios en la muestra fecal. Es destacable la elevada prevalencia de especies de microsporidios observada en los pacientes VIH estudiados, donde predominó E. intestinalis.
Microsporidioses are considered emerging and opportunistic infections in immunocompromised individuals worldwide. The purpose of this study was to identify the species of intestinal microsporidia in patients with HIV-AIDS from the Servicio Autónomo Hospital Universitario de Maracaibo, Venezuela (SAHUM). Fecal samples were collected from 50 patients with confirmed diagnosis of HIV, during the years 2007 and 2008; the CD4 values were obtained from 42 patients. The samples were analyzed by separate PCRs to identify Encephalitozoon intestinalis and Enterocytozoon bieneusi. Microsporidia species showed a 36% prevalence: ten patients had Encephalitozoon intestinalis, four Enterocytozoon bieneusi and four both species. An inverse and statistically significant relationship between the CD4 count and the presence of microsporidia in the fecal sample was also found. It is remarkable the high prevalence of microsporidia species observed in the HIV patients studied, with a predominance of E. intestinalis.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Diarreia/epidemiologia , Encephalitozoon/isolamento & purificação , Encefalitozoonose/epidemiologia , Enterocytozoon/isolamento & purificação , Fezes/microbiologia , Infecções por HIV/epidemiologia , Microsporidiose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Doenças Assintomáticas , Coinfecção , Comorbidade , DNA Fúngico/análise , Diarreia/microbiologia , Encefalitozoonose/microbiologia , Infecções por HIV/imunologia , Síndrome de Emaciação por Infecção pelo HIV/epidemiologia , Hospedeiro Imunocomprometido , Microsporidiose/microbiologia , Prevalência , Venezuela/epidemiologiaRESUMO
BACKGROUND: Microsporidiosis is a life threatening opportunistic infection of AIDS patients. The infection is usually restricted to specific anatomical areas, but could become systemic depending on the involved species. Genital microsporidiosis in female patients is rare. OBJECTIVE: To report genital microsporidiosis in female AIDS patients. METHODS: Tissues samples from the genital tract (ovary, fallopian tubes and uterus) of eight deceased women who died of wasting syndrome associated to AIDS and disseminated microsporidiosis at the Institute of Tropical Medicine Pedro Kourí were collected between 1997 and 2005. Using an indirect immunohistochemistry assay the microsporidia species involved in those cases were identified. RESULTS: We report several cases of microsporidial infection of the female genital tract. Six out of eight women with the disseminated form of the disease showed the presence of microsporidia in the genital tract. Encephalitozoon cuniculi and Encephalitozoon hellem were identified in the internal lining epithelium of the fallopian tubes and endometrium. CONCLUSIONS: Microsporidia species could disseminate to other organs and become systemic in severe immunocompromised cases. To our knowledge this is the greatest number of female genital tract microsporidiosis cases so far reported in humans.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Encefalitozoonose/patologia , Doenças dos Genitais Femininos/patologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Autopsia , Vasos Sanguíneos/microbiologia , Colo do Útero/microbiologia , Progressão da Doença , Encephalitozoon/isolamento & purificação , Encephalitozoon cuniculi/isolamento & purificação , Encefalitozoonose/microbiologia , Endométrio/microbiologia , Células Epiteliais/microbiologia , Tubas Uterinas/microbiologia , Feminino , Doenças dos Genitais Femininos/microbiologia , Síndrome de Emaciação por Infecção pelo HIV/patologia , Humanos , Macrófagos/microbiologia , Especificidade de Órgãos , Esporos Fúngicos/isolamento & purificaçãoRESUMO
Microsporidia are eukaryotic, intracellular obligate parasites that infect invertebrate and vertebrate animals, and have emerged as important opportunistic parasites in AIDS patients. We used light microscopy to detect microsporidial spores in stool samples of a domestic cat confirmed as Encephalitozoon intestinalis by PCR, owned by an AIDS patient with chronic diarrhea and E. intestinalis infection. Cats can be considered hosts of E. intestinalis.