Interferon‐gamma and the induction of protective lgG2a antibodies in non‐lethal Plasmodium berghei infections of mice

Abstract

Mice treated with anti-IFN-gamma monoclonal antibodies were unable to recover from infection with an attenuated variant of P. berghei (Pb XAT) which causes non-lethal malaria in normal mice. On the other hand, treatment with anti-IL-4 monoclonal antibodies had no effect on the course of infection. IFN-gamma was produced by spleen cells in vitro during the early phase of the infection. Treatment with anti-IFN-gamma suppressed development of an anti-plasmodial IgG2a immunoglobulin isotype in the serum of infected mice whereas anti-IL-4 interfered with the IgG1 response. An IgG2a fraction of immune serum collected from mice that had recovered from Pb XAT transferred immunity to naive mice but the IgG1 fraction did not. When glutaraldehyde fixed parasitized erythrocytes were incubated with immune serum in suspension, specific IgG2a antibodies were detected by fluorescein staining on the membranes of cells infected with mature stages of parasites. These results indicate that IFN-gamma is a key to inducing B cells to produce the protective antiplasmodial IgG2a immunoglobulin isotype. Antibody-dependent cell-mediated parasite killing seems to be involved in the mechanism of recovery from infection with Pb XAT.

mRNA expression of cytokines and its impact on outcomes after infection with lethal and nonlethal Plasmodium vinckei parasites

“…The authors concluded that Th1-associated rise in endogenous TNF-α in the spleen correlates with nonlethal infection. However, contrary to present results, Waki et al (1995) have shown that IL-12 is implicated in pathogenesis instead of providing protection during lethal P. berghei NK65 infection which might be due to the difference in quantity produced, the site of its production, time during which its production is sustained, and presence of other molecules regulating its production. Unlike the Th1 cytokines, Th2 cytokines (IL-10 and IL-4) are known to suppress or downregulate inflammatory responses which are essential to control immune pathology.…”

A transient resistance to blood-stage malaria in interferon-γ-deficient mice through impaired production of the host cells preferred by malaria parasites

“…IFN-γ plays a protective role in malaria infection by inducing the activation of macrophages, which are responsible for the clearance of merozoites and parasitic erythrocytes (Yoneto et al, 2001; Su et al, 2002). It also drives humoral immunity by enhancing IgG2a production, as well as supporting cellular immunity (Waki et al, 1995). Our findings additionally indicate that IFN-γ-independent protective mechanisms successfully control mild parasitemia with PyNL observed in GKO mice, as some or even all GKO mice survived the infection (Figures 1A, 3A).…”

Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment ofPlasmodium yoeliiMerozoite Surface Protein 1 in Mice

“…IgG2a subclass prefers to bind Fc␥RI and then mediate antibody-dependent cell-mediated cellular cytotoxicity, antibody-dependent cellular inhibition, and phagocytosis, but the MSP1 19 -specific IgG2a antibody has been reported not to use the Fc function for antibody-mediated protection (21,27). It may function by blocking parasite invasion or inhibiting MSP1 processing, which is required for erythrocyte entry (3,28).…”