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

Abstract

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-γ , 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 (H2 b or H2 d ) 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, we observed 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. gondii.

Novel Approaches Reveal that Toxoplasma gondii Bradyzoites within Tissue Cysts Are Dynamic and Replicating EntitiesIn Vivo

“…2B and C ). The proportion of these smaller cysts remains stable between weeks 5 and 8, well into the chronic phase, suggesting that continuous low-level reactivation must occur in the CBA/J background as has been previously reported ( 64 , 72 – 74 ). Examination of other permissive (C57B/6) or less-permissive (BALB/c) backgrounds may provide insights into the reactivation/reseeding processes and the impact of the host immune context on these processes ( 64 , 72 – 74 ).…”

Pathological changes in acute experimental toxoplasmosis with Toxoplasma gondii strains obtained from human cases of congenital disease

“…Therefore, we suggest that the intrinsic aspects of T. gondii strains play a key role in the induction of inflammatory bowel injuries. This conclusion is also supported by several authors who found different degrees of intestinal damage using different strains (Djurković-Djaković et al, 2006;Dubey et al, 2012a;Fux et al, 2003;Resende et al, 2008;Smiley et al, 2005).…”

Toxoplasma gondii Soluble Tachyzoite Antigen Triggers Protective Mechanisms against Fatal Intestinal Pathology in Oral Infection of C57BL/6 Mice

“…gondii infection, such as 10 cysts by oral route induced less inflammation than 60 cysts [22]. However, so low doses of Toxoplasma, as 4 or one single-tissue cyst also induce pathology and inflammatory cytokines production [23-25]. In our investigation, in addition to the beneficial effect of the reduced parasitism, other mechanisms induced by STAg are involved in the control of the exacerbated immune response.…”