The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain

Cepas de Toxoplasma gondii que apresentam o gen??tipo I/III s??o associadas a toxoplasmose ocular adquirida em humanos. No presente trabalho, n??s utilizamos um modelo da doen??a em camundongos para caracterizar mecanismos imunol??gicos envolvidos na resist??ncia do hospedeiro ?? infec????o por aquelas cepas. Escolhemos as cepas D8, G2 e P-Br, que causam infec????o cr??nica em camundongos, semelhante ?? toxoplasmose humana. Camundongos deficientes em MyD88, IFN-G e IL-12 foram suscept??veis a infec????es com todas as tr??s linhagens do parasita. Esses dados indicam a import??ncia de mecanismos inatos no controle da infec????o. Por outro lado, o hapl??tipo do MHC n??o influenciou na resist??ncia/susceptibilidade, na medida em que linhagens de camundongos com um mesmo "background'' gen??tico, mas diferentes hapl??tipos de MHC (H2b e H2d) apresentam o ??ndice de mortalidade e n??mero de cistos semelhantes ap??s a infec????o com aquelas cepas do parasita. Em contraste, o "background'' gen??tico de C57BL/6, mas n??o o hapl??tipo de MHC, foi cr??tico para o desenvolvimento de inflama????o intestinal causada pelas cepas estudadas. Finalmente, com rela????o aos mecanismos efetores, observamos que linf??citos B e T CD8+ controlam a sobreviv??ncia ap??s infec????o. Por outro lado, a ativa????o da enzima ??xido n??trico sintase induzida foi um fator importante para controle do n??mero de cistos cerebrais em camundongos infectados com cepas do Tipo I/III. Esses achados s??o relevantes para o melhor entendimento dos mecanismos imunol??gicos envolvidos na prote????o e patog??nese durante infec????o com T. gondii.Toxoplasma gondii strains displaying the Type I/III genotype are associated with acquired ocular toxoplasmosis in humans. Here, we used a mice model to characterize some immunological mechanisms involved in host resistance to infection with such strains. We have chosen the Type I/III strains D8, G2 and P-Br, which cause a chronic infection in mice that resembles human toxoplamosis. Mice deficient of molecules MyD88, IFN-???, and IL-12 were susceptible to all three parasite strains. This finding indicates the importance of innate mechanisms in controlling infection. On the other hand, MHC haplotype did not influenced resistance/susceptibility; since mice lineages displaying a same genetic background but different MHC haplotypes (H2b or H2d) developed similar mortality and cyst numbers after infection with those strains. In contrast, the C57BL/6 genetic background, and not MHC haplotype, was critical for development of intestinal inflammation caused by any of the studied strains. Finally, regarding effector mechanisms, weobserved that B and CD8+ T lymphocytes controlled survival,whereas the inducible nitric oxide synthase influenced cyst numbers in brains of mice infected with Type I/III strains. These findings are relevant to further understanding of the immunologic mechanisms involved in host protection and pathogenesis during infection with T. gondi