Immunoregulation of malarial infection: balancing the vices and virtues

Malaria continues to extract an incalculable cost on human morbidity and mortality throughout tropical and subtropical regions of the world, and effective control measures are urgently needed. Despite considerable efforts in recent years to develop subunit vaccines targeted at various stages of the Plasmodium life-cycle, the commercial availability of a vaccine is still a distant prospect. One of the underlying difficulties hindering successful vaccine design is our incomplete knowledge of the precise type(s) of immune response to aim for, and then how to achieve it. A greater appreciation of the mechanisms of protective immunity, on the one hand, and of immunopathology, on the other, should provide critical clues on how manipulation of the immune system may best be achieved. Ten years have passed since the identification of the Th1/Th2 paradigm for distinguishing CD4+ T cells according to cytokine secretion patterns which determine their function. This review summarises our progress towards understanding the broad spectrum of immune responsiveness to the blood stages of the malaria parasite during experimental infections in mice and highlights the way in which examination of rodent malarias provides a powerful tool to dissect the interaction of Th1 and Th2 cells during an immune response to an infectious disease agent. It is proposed that the pliability of rodent systems for investigating immunoregulation provides valuable insight into the balance between protection and pathology in human malaria and throws light on the factors involved in the modulation of vaccine-potentiated immunity.