Complement Contributes to Protective Immunity against Reinfection byPlasmodium chabaudi chabaudiParasites

Abstract

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-␥) 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-␥ in response to malarial antigens in vitro, intracellular cytokine staining of spleen cells ex vivo showed no difference in the numbers of IFN-␥ ؉ 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.

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

“…As noted above, different protocols have yielded different effects of C1q deficiency on the immune response (24,29,30). For this reason, we directly tested the role of the classic pathway in our experimental system and included Cr2 −/− mice for comparison.…”

“…However, lack of C1q was compatible with a normal or even higher Ab response against certain Ags in some situations (24,30), and to ascertain that C1q was important in our system, we first analyzed the Ab responses to a wide range of SRBC doses (Fig. 1).…”

“…The most direct support for this is the reduced HA titers against high doses of SRBCs administered to C1qA −/− mice (29). Responses to malaria parasites or West Nile virus in C1q-deficient mice were much less affected than responses to SRBCs, and were even higher than in WT mice in some cases (24,30).…”

The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

“…In line with the role of C1q in complement activation, its deficiency causes increase in host susceptibility to microbial infections, e.g., Salmonella infections (7), malaria reinfection (8), and polymicrobial peritonitis (9). MBL deficiency is associated with increased susceptibility to childhood infections (10).…”

Heavily Isotype-Dependent Protective Activities of Human Antibodies against Vaccinia Virus Extracellular Virion Antigen B5

“…C3 deficiency in humans typically results in recurrent pyogenic bacterial infections (13,32,78). Several reports now indicate that a genetic deficiency in C1q in humans results in an enhanced susceptibility to pathogens (15,32,96,106), and if individuals survive these infections, they develop lupus-like autoimmune disease (12,74,80,102,103).…”