Protective immunity to erythrocytic Plasmodium chabaudi AS infection involves IFNγ-mediated responses and a cellular infiltrate to the liver

Abstract

IFNγ receptor (IFNγR) deficient mice and IL-4 deficient mice were infected with blood-stage Plasmodium chabaudi AS in order to analyse the role of Th1 (IFNγ) and Th2 (IL-4)-associated cytokines in the development of protective immunity to the parasite. A high mortality rate and failure to reduce the primary parasitaemia to subpatent levels was observed in the IFNγR deficient mice. IL-4 deficient mice controlled a primary P. chabaudi AS infection in a similar manner to control mice and no mortality was observed. IFNγR deficient mice had a reduction in parasite-specific IgG and a significantly increased level of total IgE compared to control mice. There was no reduction in the level of parasite-specific IgG in IL-4 deficient mice. Cytological analysis of the cells present in the spleen and liver during the primary parasitaemia revealed a reduction in the numbers of lymphocytes, monocytes and polymorphonuclear (PMN) cells in the liver at the peak of parasitaemia in both IFNγR deficient mice and IL-4 deficient mice compared to control mice. Adoptive transfer studies demonstrated that cells isolated from the liver at day 11 post-infection could confer some protective immunity to P. chabaudi AS infection.