title: More than just immune evasion: Hijacking complement by Plasmodium falciparum.
abstract: Malaria remains one of the world's deadliest diseases. Plasmodium falciparum is responsible for the most severe and lethal form of human malaria. P. falciparum's life cycle involves two obligate hosts: human and mosquito. From initial entry into these hosts, malaria parasites face the onslaught of the first line of host defence, the complement system. In this review, we discuss the complex interaction between complement and malaria infection in terms of hosts immune responses, parasite survival and pathogenesis of severe forms of malaria. We will focus on the role of complement receptor 1 and its associated polymorphisms in malaria immune complex clearance, as a mediator of parasite rosetting and as an entry receptor for P. falciparum invasion. Complement evasion strategies of P. falciparum parasites will also be highlighted. The sexual forms of the malaria parasites recruit the soluble human complement regulator Factor H to evade complement-mediated killing within the mosquito host. A novel evasion strategy is the deployment of parasite organelles to divert complement attack from infective blood stage parasites. Finally we outline the future challenge to understand the implications of these exploitation mechanisms in the interplay between successful infection of the host and pathogenesis observed in severe malaria.
authors: Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Helmholtzstraße 20, Ulm, Germany. Electronic address: christoph.schmidt@uni-ulm.de.
authors: Christoph Q
authors: CQ
authors: Schmidt
authors: Department of Medical Biology, University of Melbourne and Division of Infection and Immunity, The Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia.
authors: Alexander T
authors: AT
authors: Kennedy
authors: Department of Medical Biology, University of Melbourne and Division of Infection and Immunity, The Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia. Electronic address: tham@wehi.edu.au.
authors: Wai-Hong
authors: WH
authors: Tham
mesh_terms: D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000235:genetics; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins / Q000235:genetics / Q000276:immunology*; D017242:Complement Factor H / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D057131:Immune Evasion; D008018:Life Cycle Stages / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D011110:Polymorphism, Genetic; D011951:Receptors, Complement / Q000235:genetics / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D011951:Receptors, Complement; D017242:Complement Factor H
keywords: Complement; Complement receptor 1; Evasion strategies; Parasite invasion; Plasmodium falciparum; Severe malaria pathogenesis