Down-regulation of murine susceptibility to cerebral malaria by inoculation with third-stage larvae of the filarial nematode Brugia pahangi

Abstract

In areas where malaria is endemic, helminthic infections, caused by intestinal or filarial parasites, commonly coexist with malaria in the same individual. This study investigates the course of Plasmodium berghei malaria infection in CBA/J mice inoculated with irradiated attenuated 3rd-stage larvae (L3) of Brugia pahangi. Peripheral eosinophil counts, serum IgE levels and cytokine production revealed that the filarial antigen induced T-helper type 2 (Th2) cell predominance in these mice, which protected them against the development of cerebral malaria. These mice significantly prolonged their survival, compared with the control mice after P. berghei infection. All of the mice not inoculated with irradiated L3 died within 12 days with acute neurological manifestations unrelated to the level of parasitaemia after infection of P. berghei. Conversely, most of the inoculated mice lived more than 3 weeks following infection with P. berghei, dying in the fourth week of severe anaemia and overwhelming parasitaemia. This suggests that Th2-dominant responses lead to the down-regulation of susceptibility to murine cerebral malaria.