Deceiving and escaping complement – the evasive journey of the malaria parasite

During its life cycle, Plasmodium, the malaria parasite, is exposed to the human and mosquito complement systems. Early experiments demonstrated that activation of complement can pose a serious threat to parasites, but recent studies revealed complement-evasion mechanisms important for parasite survival. Blood-stage parasites and gametes recruit regulators to neutralize human complement activation, while ookinetes inhibit mosquito complement by disrupting epithelial nitration in response to midgut invasion. Here we provide an in-depth overview of the evasion mechanisms currently known and speculate on the existence of others not yet identified. Finally, we discuss how these mechanisms could provide novel targets for urgently needed malaria vaccines and therapeutics. Different developmental stages of malaria parasites are exposed to the human and/or mosquito complement systems, but they seem to be mostly unaffected as Plasmodium parasites complete their life cycle, are transmitted, and cause infection.Recent studies have shed light on how malaria parasites actively neutralize the complement systems. These evasion mechanisms are important for parasite survival.It remains unclear how some parasite stages evade complement attack.Complement activation may be an important effector mechanism of RTS,S, the only currently approved malaria vaccine, and may therefore contribute to its efficacy.