Expressão de RNAm TLR 2, TLR 4 e citocinas em infecção experiemental por cepas Trypanosoma cruzi de diferentes origens
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Data
2011-11-02
Autores
Picka, Mariele Cristina Modolo [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Receptores Toll-like (TLRs), em células apresentadoras de antígenos, têm importante papel no reconhecimento microbiano e no desenvolvimento da resposta imune adaptativa. Na infecção por T. cruzi, a imunidade celular, medida pela atividade de citocinas pró-inflamatórias, como IL-12 e IFN-γ, do perfil Th1, associadas ao TNF-α, reduz a carga parasitária na fase crônica. Simultaneamente, a IL-4 e a IL-10, do perfil Th2, são responsáveis por amortecer os fortes efeitos da ação pró-inflamatória. Características do parasita, como variação antigênica e diversidade genética das linhagens de T. cruzi, também têm influência na resposta imune do hospedeiro. Assim, este estudo teve como objetivos, em infecção experimental com cepas de diferentes origens de T. cruzi: fazer a caracterização molecular das cepas; determinar os momentos evolutivos da infecção (curva de parasitemia e sobrevida) e verificar a expressão gênica relativa de TLR 2, TLR 4, IL-12p40, IFN-γ,TNF-α, IL-10 e IL-4 em cada momento da infecção. Para isso, foram utilizadas duas cepas de T. cruzi isoladas de pacientes chagásicos crônicos, ZMC e JLP, e a cepa Y de T. cruzi. Camundongos machos Balb/C foram infectados com 104 tripomastigotas/animal e distribuídos em: G1, infectados com a cepa Y; G2, infectados com a cepa ZMC; e G3, infectados com a cepa JLP de T. cruzi. Os momentos para a determinação da expressão gênica das variáveis estudadas foram definidos segundo curva de parasitemia e de sobrevida previamente realizadas: M1: 24 h p.i.; M2: início da fase aguda; M3: fase aguda; M4:momento da queda importante e de manutenção da parasitemia e M5: momento final, determinado pela curva de sobrevida. Todas as cepas foram classificadas no grupo TCII, apesar de apresentarem comportamentos distintos em relação ao número de parasitas...
Toll-like receptors (TLRs), in antigen-presenting cells, play an important role in microbial recognition and adaptive immune response development. In T. cruzi infection, cellular immunity, mediated by the activity of proinflammatory cytokines such as IL-12 and IFN-γ, of the Th1 profile, associated with TNF-α, reduces parasite load in the chronic phase. Simultaneously, IL-4 and IL-10, of the Th2 profile, are responsible for controlling the strong proinflammatory effects of Th1 profile. Parasite characteristics, such as antigen variation and genetic diversity of T. cruzi strains, also influence host immune response. Hence, by using experimental infection with T. cruzi strains of different origins, this study aimed at: performing the molecular characterization of the strains; determining the evolutive moments of the infection (parasitemia and survival curve) and analyzing the relative gene expression of TLR 2, TLR 4, IL-12p40, IFN-γ,TNF-α, IL-10 and IL-4 at each moment of infection. To that end, two T. cruzi strains, ZMC and JLP, isolated from chronic chagasic patients, and the Y strain of T. cruzi were used. Male Balb/C mice were infected with 104 trypomastigotes/animal and distributed into: G1, infected with the Y strain; G2, infected with the ZMC strain; and G3, infected with the JLP of T. cruzi. The moments for determination of gene expression of the studied variables were defined according to the curve of parasitemia and survival that was previously performed: M1: 24 h p.i.; M2: beginning of the acute phase; M3: acute phase; M4: moment of important decrease and maintenance of parasitemia and M5: final moment, determined by the survival curve. All the strains were classified in the TCII group although they showed different behaviors in relation to the number of circulating parasites, day of the acute phase peak and... (Complete abstract click electronic access below)
Toll-like receptors (TLRs), in antigen-presenting cells, play an important role in microbial recognition and adaptive immune response development. In T. cruzi infection, cellular immunity, mediated by the activity of proinflammatory cytokines such as IL-12 and IFN-γ, of the Th1 profile, associated with TNF-α, reduces parasite load in the chronic phase. Simultaneously, IL-4 and IL-10, of the Th2 profile, are responsible for controlling the strong proinflammatory effects of Th1 profile. Parasite characteristics, such as antigen variation and genetic diversity of T. cruzi strains, also influence host immune response. Hence, by using experimental infection with T. cruzi strains of different origins, this study aimed at: performing the molecular characterization of the strains; determining the evolutive moments of the infection (parasitemia and survival curve) and analyzing the relative gene expression of TLR 2, TLR 4, IL-12p40, IFN-γ,TNF-α, IL-10 and IL-4 at each moment of infection. To that end, two T. cruzi strains, ZMC and JLP, isolated from chronic chagasic patients, and the Y strain of T. cruzi were used. Male Balb/C mice were infected with 104 trypomastigotes/animal and distributed into: G1, infected with the Y strain; G2, infected with the ZMC strain; and G3, infected with the JLP of T. cruzi. The moments for determination of gene expression of the studied variables were defined according to the curve of parasitemia and survival that was previously performed: M1: 24 h p.i.; M2: beginning of the acute phase; M3: acute phase; M4: moment of important decrease and maintenance of parasitemia and M5: final moment, determined by the survival curve. All the strains were classified in the TCII group although they showed different behaviors in relation to the number of circulating parasites, day of the acute phase peak and... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Chagas, Doença de, Doenças transmissiveis, Tripanossoma cruzi
Como citar
PICKA, Mariele Cristina Modolo. Expressão de RNAm TLR 2, TLR 4 e citocinas em infecção experiemental por cepas Trypanosoma cruzi de diferentes origens. 2011. 71 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Medicina de Botucatu, 2011.