Secreted Antibody Is Required for Immunity toPlasmodium berghei

Abstract

Infection with Plasmodium berghei is lethal to mice, causing high levels of parasitemia, severe anemia, and death. However, when mice are treated with antimalarial drugs during acute infection, they have enhanced immunity to subsequent infections. With this infection and cure model of immunity, we systematically examined the basis of adaptive immunity to infection using immunodeficient mice. In order to induce adaptive immunity, mice were infected with blood-stage parasites. When the mice developed 2 to 3% parasitemia, they were treated with chloroquine to cure the infection. These convalescent mice were then challenged with homologous blood-stage parasites. Immunized wild-type mice were able to control the level of infection. In contrast, mice lacking mature B cells and T cells were unable to control a challenge infection, indicating the critical role of lymphocytes in immunity to P. berghei. Furthermore, mice lacking secreted antibody were unable to control the level of parasitemia following a challenge infection. Our results indicate that secreted antibody is a requirement for immunity to P. berghei.Each year there are approximately 500 million cases of malaria worldwide, resulting in 2 to 3 million deaths, primarily in children in sub-Saharan Africa (42). Malaria is caused by infection with one of four protozoan Plasmodium species: P. falciparum, P. vivax, P. malariae, and P. ovale. P. falciparum is responsible for the majority of severe disease, which can manifest itself in anemia, cerebral malaria, organ failure, and death. Repeated infection and treatment of individuals in areas of malaria endemicity eventually induce a level of immunity that limits morbidity and results in chronic infection with low levels of parasitemia (41). A fully effective vaccine that reduces parasite burden and severe disease has not been developed.Murine models of malaria have long been used to examine the immune response to Plasmodium parasites and to understand the host factors required for the development of immunity. P. berghei infection in mice is lethal, causing high levels of parasitemia, severe anemia, and body weight loss. However, mice can become resistant to subsequent infections by treatment with antimalarial drugs during acute infection (27). This is known as the infection and cure model, and mice that develop this immunity mimic the human experience of disease in that they are reinfected but experience low-level patent parasitemia and survive. However, it takes years to establish this level of immunity in humans (36), while in mice it is accomplished by only one infection and drug cure, which provides long-lasting protection (12,13,48). An understanding of the basis of rodent immunity to blood-stage infection will help to direct future vaccine approaches.The fact that immunity induced by infection and cure is long-lasting suggests that the adaptive immune system is required for immunity. Evidence from previous work indicates a role for B and T cells in immunity. Mice lacking both mature B and T cells (SCID mice) (6)...

CD19(+) B Cells Confer Protection against Experimental Cerebral Malaria in Semi-Immune Rodent Model

“…In contrast, other studies have reported that parasite burden does not appear to play a pivotal role in the development of ECM in the Pb A model [84]–[86], [16], [87]. It was reported that malaria specific antibodies inhibited parasite proliferation [88]. In our study, 3-cure mice, having lower parasitemia and higher malaria specific antibodies than 0-cure counterparts, did not develop ECM during the course of infection.…”

Within-Host Selection of Drug Resistance in a Mouse Model of Repeated Incomplete Malaria Treatment: Comparison between Atovaquone and Pyrimethamine

“…The acquisition of immunity to P. berghei in mice is well documented. Thus, while primary P. berghei infections in white mice invariably resulted in 100% mortality, a second infection after cure with an antimalarial drug is usually milder, as characterized by the survival of the majority of infected mice (16)(17)(18). The manifestation of such acquired immunity to P. berghei, however, was not observed in our RICT model.…”

Animal Models of Anemia of Inflammation

“…P. chabaudi infected red blood cells injected IP causes anemia after about five days that reaches a nadir at 10 days31,32. P. berghei causes severe anemia but is rapidly fatal without treatment33,34. P. yoelii infects mice, has not been shown to be a human pathogen and different strains produce differing severities of anemia and mortality35.…”