Avalia??o da express?o de receptores da imunidade inata em linhagens de camundongos suscet?veis e resistentes a infec??o pelo Schistosoma mansoni

• Main Author: Lima, Janete Cunha
• Other Authors: 02351506731
• Language: Portuguese
• Published: Programa de P?s-Gradua??o em Biologia Parasit?ria 2017
• Subjects: CNPQ::CIENCIAS BIOLOGICAS: BIOLOGIA PARASIT?RIA; Schistosoma mansoni; Imunidade Inata; Receptores; Citocinas
• Online Access: https://repositorio.ufrn.br/jspui/handle/123456789/22182

Submitted by Automa??o e Estat?stica ([e-mail]) on 2017-02-22T20:13:29Z No. of bitstreams: 1 JaneteCunhaLima_DISSERT.pdf: 3013582 bytes, checksum: d401198755cf83fbccff88970e69f861 (MD5) === Approved for entry into archive by Arlan Eloi Leite Silva ([e-mail]) on 2017-03-08T21:51:16Z (GMT) No. of bitstreams: 1 JaneteCunhaLima_DISSERT.pdf: 3013582 bytes, checksum: d401198755cf83fbccff88970e69f861 (MD5) === Made available in DSpace on 2017-03-08T21:51:16Z (GMT). No. of bitstreams: 1 JaneteCunhaLima_DISSERT.pdf: 3013582 bytes, checksum: d401198755cf83fbccff88970e69f861 (MD5) Previous issue date: 2016-01-29 === O presente estudo objetivou avaliar a express?o dos receptores da imunidade inata em linhagens de camundongos suscet?veis e resistentes ? infec??o pelo Schistosoma mansoni. Cerca de 30 cerc?rias da cepa LE do S. mansoni foram inoculadas por via subcut?nea em camundongos machos das linhagens Balb/c, C57BL/6 e Swiss. Duas, sete, 12 e 16 semanas ap?s a infec??o (SAI) os camundongos foram mortos e quando poss?vel foram avaliados os seguintes par?metros: parasitismo (por meio de perfus?o hep?tica), oograma, presen?a de granulomas hep?ticos, e express?o do RNA mensageiro (RNAm) de citocinas da imunidade inata (IL-1?, IL-6, IL-10, IL-12p35, IL-18 e TNF-?), dos receptores do tipo Toll (TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9), dos receptores do tipo Nod (NALP1 e NALP3) e mol?culas adaptadoras (Myd88, ASC, Caspase-1) em tecido hep?tico, por meio de PCR em tempo real. Camundongos Balb/c e C57BL/6 apresentaram sobreviv?ncia de 70%, enquanto camundongos Swiss apresentaram sobreviv?ncia de 100%, quando avaliados at? 16 SAI. Em duas SAI os camundongos Swiss apresentaram maior express?o do RNAm de NLRP1, NLRP3, Caspase-1, IL-1? e IL-18, quando comparados aos Balb/c e C57BL/6. Os animais das linhagens Balb/c e C57BL/6 apresentaram maior express?o do RNAm de TLR2, TLR3, TLR5, NLRP3 e ASC em sete SAI, quando comparados aos Swiss. Em adi??o, a linhagem Balb/c apresentou express?o aumentada do RNAm de TLR6, TLR7, TLR9, Myd88, NLRP1 e TNF-?. Ademais, camundongos Swiss apresentam menor quantidade de parasitos adultos no sistema porta hep?tico e menor quantidade de ovos no fragmento ?leo distal, em sete e 12 SAI, quando comparados aos C57BL/6 e Balb/c. Em conclus?o, os camundongos C57BL/6 e Balb/c apresentam express?o elevada dos receptores TLRs e NLRs em sete SAI (in?cio da oviposi??o), sugerindo maior suscetibilidade a infec??o, com consequente aumento na taxa de mortalidade nestes animais. Outrossim, camundongos Swiss apresentam acentuado perfil inflamat?rio inicial (em duas SAI), o que poderia auxiliar no controle do parasitismo. E a supress?o da ativa??o dos receptores e citocinas da imunidade inata, em sete SAI, poderiam ocasionar menor mortalidade e maior resist?ncia ? infec??o neste per?odo. === This study aimed to evaluate innate immune receptors expression in susceptible and resistant mouse strains to infection with Schistosoma mansoni. About 30 S. mansoni cercariae, LE strain, were inoculated subcutaneously into Balb/c, C57BL/6 and Swiss male mice. Two, seven, 12 and 16 weeks after infection (WAI) mice were euthanized and when possible evaluated the following parameters: parasitism by hepatic portal system perfusion, oogram, presence of hepatic granulomas, and cytokines of innate immunity (IL-1?, IL-6, IL-10, IL-12p35, IL-18 and TNF-?) mRNA expression, innate immunity Toll-like receptor (TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9) mRNA expression, Nod-like receptor (NALP1 and NALP3), and adapter molecules (Myd88, ASC, and Caspase-1) mRNA expression in liver tissue, by Real-time PCR. Balb/c and C57BL/6 mice showed survival of 70%, while Swiss mice showed 100% survival when evaluated by 16 WAI. In two WAI Swiss mice showed higher NLRP1, NLRP3, caspase-1, IL-1? and IL-18 mRNA expression when compared to Balb/c and C57BL/6. Balb/c and C57BL/6 mice showed higher TLR2, TLR3, TLR5, NLRP3 and ASC mRNA expression in seven WAI when compared to the Swiss. In addition, Balb/c mice showed increased TLR6, TLR7, TLR9, MyD88, NLRP1 and TNF-? mRNA expression. Moreover, Swiss mice have a lower number of adult parasites in the hepatic portal system and fewer eggs in the distal ileum fragment in seven and 12 WAI when compared to Balb/c and C57BL/6. In conclusion, C57BL/6 and Balb/c mice showed high TLRs and NLRs receptors mRNA expression in seven WAI (oviposition beginning), suggesting intensify susceptibility to infection, with consequent increase in the mortality rate in these animals. Furthermore, Swiss mice exhibited increase initial inflammatory profile (in two WAI), which could assist in the control of parasitism. And the mRNA activation suppression of cytokines and receptors of innate immunity, in seven WAI, could cause lower mortality and greater resistance to infection during this period.