Malária grave murina: análise histopatológica e imunológica em tecido cerebral e pulmonar de camundongos C57BL/ imunizados com parasitos vivos de fase sanguínea de Plasmodium berghei (Cepas ANKA e NK65) e desafiados com Plasmodium berghei ANKA

Abstract

The use of ultra-low doses of live blood stage parasites is one of several strategies used to induce anti-malarial immunity. Although this method apparently induces cross-species and strain-transcendent immune response, there are two points that need to be explored: 1) no study has assessed whether immunization with live low virulence parasites is able to protect against the development of severe malaria, including cerebral malaria; 2) African children often develop severe malaria only after re-exposure to highly virulent parasites. Thus, the relationship between the use of live parasites and possible development of serious infections needs to be investigated. To clarify these two points, C57BL/6 mice were immunized once or twice with 10³ erythrocytes infected with P. berghei NK65 or P. berghei ANKA, and subsequently challenged with 10^5 P. berghei ANKA-parasitized erythrocytes. After the first immunization, only P. berghei NK65 immunized animals showed positive levels of IgG antibodies, which recognizes both homologous and heterologous antigen. In animals immunized only once, both brain and lungs exhibited fewer regions with accumulation of red blood cells and inflammation, when compared to control group or twice-immunized animals. Regardless of immunization protocols, all of the mice exhibit controlled development of P. berghei ANKA blood parasitemia. However, only P. berghei NK65 immunized animals remained alive 30 days after the being challenged with P. berghei ANKA. The TNF-α levels, on both brain and lungs, tended to rise in relation to IFN-ꝩ in animals undergoing two cycles of immunizations, which might reflect the higher tissue damage observed in these animals. However, the patterns of pro and anti-inflammatory cytokines present do not explain the observed mortality and survival rate in animals immunized with P. berghei ANKA and P. berghei NK65, respectively.