The impact of Plasmodium-driven immunoregulatory networks on immunity to malaria

Malaria, caused by infection with Plasmodium parasites, drives multiple regulatory responses across the immune landscape. These regulatory responses help to protect against inflammatory disease but may in some situations hamper the acquisition of adaptive immune responses that clear parasites. In addition, the regulatory responses that occur during Plasmodium infection may negatively affect malaria vaccine efficacy in the most at-risk populations. Here, we discuss the specific cellular mechanisms of immunoregulatory networks that develop during malaria, with a focus on knowledge gained from human studies and studies that involve the main malaria parasite to affect humans, Plasmodium falciparum. Leveraging this knowledge may lead to the development of new therapeutic approaches to increase protective immunity to malaria during infection or after vaccination. Malaria remains a devastating human disease. Although malaria vaccines are available, their limited efficacy and protective duration are problematic. In this Review, the authors discuss how immunoregulatory networks that likely develop to prevent disease during malaria may also impede prevention and control measures.