Complement contributes to protective immunity against reinfection by Plasmodium chabaudi chabaudi parasites.
We have studied the impact of deficiency of the complement system on the progression and control of the erythrocyte stages of the malarial parasite Plasmodium chabaudi chabaudi. C1q-deficient mice and factor B- and C2-deficient mice, deficient in the classical complement pathway and in both the alternative and classical complement activation pathways, respectively, exhibited only a slight delay in the resolution of the acute phase of parasitemia. Complement-deficient mice showed a transiently elevated level of gamma interferon (IFN-gamma) in the plasma at the time of the acute parasitemia compared with that of wild-type mice. Although there was a trend for increased precursor frequencies in CD4(+) T cells from C1q-deficient mice producing IFN-gamma in response to malarial antigens in vitro, intracellular cytokine staining of spleen cells ex vivo showed no difference in the numbers of IFN-gamma(+) splenic CD4(+) and CD8(+) cells. In contrast, C1q-deficient animals were significantly more susceptible to a second challenge with the same parasite. C1q-deficient animals showed a reduced level of anti-malarial immunoglobulin G2a (IgG2a) antibody 100 days after primary infection. However, following a significantly higher parasitemia, C1q-deficient mice had increased levels of IgM and IgG2a anti-malarial antibodies. In summary, this study indicates that while complement plays only a minor role in the control of the acute phase of parasitemia of a primary infection, it does contribute to parasite control in reinfection.
Taylor
P R
PR
Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Campus, London W12 0NN, United Kingdom.
Seixas
E
E
Walport
M J
MJ
Langhorne
J
J
Botto
M
M
D000208:Acute Disease; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000172:deficiency / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D016788:Plasmodium chabaudi / Q000276:immunology / Q000472:pathogenicity*; D055502:Secondary Prevention
D000913:Antibodies, Protozoan; D015847:Interleukin-4; D007371:Interferon-gamma; D003165:Complement System Proteins