RESUMO
Cryptosporidium infects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure. Cryptosporidium parvum virus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored by Cryptosporidium spp. Here we show that intestinal epithelial conditional Ifnar1-/- mice (deficient in type I IFN receptor) are resistant to C. parvum infection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. Whereas C. parvum infection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-C. parvum defense and Cryptosporidium uses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response.
Assuntos
Criptosporidiose , Cryptosporidium parvum , Interações Hospedeiro-Parasita , Interferon Tipo I , Animais , Camundongos , Antiparasitários/metabolismo , Antiparasitários/farmacologia , Criptosporidiose/etiologia , Criptosporidiose/parasitologia , Criptosporidiose/virologia , Cryptosporidium/patogenicidade , Cryptosporidium/virologia , Cryptosporidium parvum/patogenicidade , Cryptosporidium parvum/virologia , Interações Hospedeiro-Parasita/genética , Interferon Tipo I/metabolismo , Interferon Tipo I/farmacologia , Vírus de RNA de Cadeia Dupla/metabolismoRESUMO
UNLABELLED: Cryptosporidium is a major cause of diarrheal illness mainly in children and immunocompromised adults. Disease severity ranges from asymptomatic or self-limited gastroenteritis to acute or chronic diarrhoea which may be associated with systemic features. Intracellular viruses that reside in many parasites have been incriminated in pathogenesis of diseases like trichomoniasis, leishmaniasis etc. Thus we attempted to detect and quantitate the intracellular viruses in Cryptosporidium isolates and sought to seek a relationship if any, with clinical features. Cryptosporidia in stool samples from immunocompromised patients and children were identified by microscopy and species differentiated by PCR-RFLP of 18s rRNA; further subgenotyped by sequencing of GP60 region. Copy number of dsRNA virus and 18srRNA was calculated in 56 Cryptosporidium isolates (39 C. hominis and 17 C. parvum). Viral copy number per oocyst was calculated as ratio of dsRNA virus copy number to 18s rRNA copy number. Viruses were detected in all the isolates. Mean CSpV/RNA ratio was 0.17±0.4 for C. hominis isolates compared with 0.12±0.11 for C. parvum isolates, however this difference was not statistically significant. Similarly no association of diarrhoea, vomiting, cough and fever was found with either CSpV copy number or with CSpV/rRNA ratio. KEY WORDS: Cryptosporidium, virus, immunocompromised, diarrhoea.
Assuntos
Criptosporidiose/parasitologia , Cryptosporidium/virologia , RNA Viral/genética , Vírus/isolamento & purificação , Cryptosporidium/genética , Genótipo , Humanos , RNA de Cadeia Dupla/genética , Especificidade da Espécie , Vírus/genéticaRESUMO
E relatado o diagnostico de ciclosporiase humana em Sao Paulo, SP, Brasil. Cyclospora cayetanensis foi encontrada nas fezes de um individuo atraves de exame pelo metodo de coloracao de Kinyoun modificado, com posterior esporulacao em dicromato de potassio a 2,5 por cento. Esta verificacao deve estimular a necessidade de considerar a ciclosporiase como eventual causa de disturbios gastrointestinais no pais, podendo ela ser reconhecida ate mesmo por meio de tecnica razoavelmente simples. Foi ainda lembrado que esta parasitose vem adquirindo expressividade sobretudo pelo fato de nao raramente acometer imunodeprimidos, agora cada vez mais numerosos em especial como decorrencia da infeccao pelo virus da imunodeficiencia humana (HIV), que causa a sindrome da imunodeficiencia adquirida (AIDS)