What can transgenic parasites tell us about the development of Plasmodium -specific immune responses?

Malaria infects 500 million people and kills an estimated 2·7 million annually, representing one of the most significant diseases in the world. However, efforts to develop effective vaccines have met with limited success. One reason is our lack of basic knowledge of how and where the immune system responds to parasite antigens. This is important as the early events during induction of an immune response influence the acquisition of effector function and development of memory responses. Our knowledge of the interactions of Plasmodia with the host immune system has largely been derived through in vitro study. This is a significant issue as the component parts of the immune system do not work in isolation and their interactions occur in distinct and specialized micro- and macro-anatomical locations that can only be assessed in the physiological context, in vivo. In this context, the availability of transgenic malaria parasites over the last 10 years has greatly enhanced our ability to understand and evaluate factors involved in host-parasite interactions in vivo. In this article, we review the current status of this area and speculate on what parasite transgenesis approaches will tell us about the development of Plasmodium-specific immune responses in the future.