Immune responses mediating survival of naive BALB/c mice experimentally infected with lethal rodent malaria parasite, Plasmodium yoelii nigeriensis

The rodent malaria parasite, Plasmodium yoelii nigeriensis is known to caus e fatal malaria infections in BALB/c mice. However, we found that nearly 5 % of inbred BALB/c mice could overcome primary infections initiated with le thal inoculum of P.y. nigeriensis asexual blood-stages, without any experim ental intervention. These 'survivor' mice developed peak parasitemia levels of about 5 % and successfully resolved their infections in about two weeks time; infected blood collected during the descending phase of infection in these mice and subinoculated in naive recipients resulted in a normal leth al course of infection. Typically, the parasites in survivor mice looked 's ick' compared to those in the susceptible mice. In experiments to define te mporal basis of this protection, we found that purified splenic B cells iso lated from such a survivor mouse, plus T cells from an infected or naive mo use, could adoptively transfer this protection to an X-irradiated, naive mo use against a lethal parasite challenge. Purified T cells or B cells alone from the survivor mouse donor provided no protection to the X-irradiated, n aive recipient. Passive transfer of sera collected from survivor mice anima ls a week after recovery from infection was also able to substantially alte r the course of preestablished P.y. nigeriensis infection. These findings a re discussed in the light of recent reports on the genetic control of blood parasitemia in mouse malaria models. In the generally lethal malaria infec tions such as those caused by P.y. nigeriensis in mice and by Plasmodium fa lciparum in naive children, it is not clear what constitutes a protective i mmune response in cases which survive primary infections without any experi mental or therapeutic intervention. An understanding of these mechanisms an d their regulation would help design better vaccination strategies. (C) 200 0 Editions scientifiques et medicales Elsevier SAS.