Secreted antibody is required for immunity to Plasmodium 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.

FIG. 1.

Course of infection in immunized C57BL/6 mice. C57BL/6 mice in the immunized group (n = 6) were infected with P. berghei by i.p. injection of iRBCs. Mice in the nonimmunized group (n = 3) were mock infected by i.p. injection of PBS. All mice were treated with chloroquine (chl) when parasitemia reached 2 to 3% in the immunized group. Following an incubation of at least 40 days, all mice were challenged, and parasitemia was monitored on the days indicated. Immunized mice developed patent parasitemia following challenge but were able to control the infection. Mice in the nonimmunized group were unable to control the infection. Data are representative of results from seven independent experiments. The asterisks indicate a significant difference in parasitemia (P < 0.05) between groups. The arrows indicate infection or challenge at the times indicated.

FIG. 2.

Course of infection in immunized mice lacking B and T cells. Both C57BL/6 (n = 5) and RAG1^−/− (n = 6) mice were immunized and monitored as described for the immunization model. All mice were treated with chloroquine (chl) when parasitemia reached 2 to 3%. Following challenge, RAG1^−/− mice were unable to control infection. Data are representative of results from three independent experiments. The asterisks represent a significant difference in parasitemia (P < 0.05) between groups. The arrows indicate infection or challenge at the times indicated.

FIG. 3.

Passive protection of naïve C57BL/6 mice against P. berghei. Serum samples were collected from immunized mice or nonimmunized mice. Serum was injected i.p. into naïve C57BL/6 recipients (three mice per group) on days 0, 3, and 6. Passively immunized mice were challenged i.p. with 1 × 10⁶ iRBCs on day 0, and parasitemia was monitored on the days indicated.

FIG. 4.

Course of infection in immunized mice lacking secreted antibody. Both C57BL/6 (n = 6) and AID^−/− μs^−/− (n = 3) mice were immunized and monitored as described for the immunization model. All mice were treated with chloroquine (chl) when parasitemia reached 2 to 3%. Following challenge, AID^−/− μs^−/− mice were unable to control infection. Data are representative of results from two independent experiments. The asterisks represent a significant difference in parasitemia (P < 0.05) between groups. The arrows indicate infection or challenge at the times indicated.