title: Platelets activate a pathogenic response to blood-stagePlasmodiuminfection but not a protective immune response.
abstract: Clinical studies indicate that thrombocytopenia correlates with the development of severe falciparum malaria, suggesting that platelets either contribute to control of parasite replication, possibly as innate parasite killer cells or function in eliciting pathogenesis. Removal of platelets by anti-CD41 mAb treatment, platelet inhibition by aspirin, and adoptive transfer of wild-type (WT) platelets to CD40-KO mice, which do not control parasite replication, resulted in similar parasitemia compared with control mice. Human platelets at a physiologic ratio of 1 platelet to 9 red blood cells (RBCs) did not inhibit the in vitro development or replication of blood-stagePlasmodium falciparumThe percentage ofPlasmodium-infected (iRBCs) with bound platelets during the ascending parasitemia inPlasmodium chabaudi- andPlasmodium berghei-infected mice and the 48-hour in vitro cycle ofP falciparumwas <10%.P chabaudiandP bergheiiRBCs with apoptotic parasites (TdT+) exhibited minimal platelet binding (<5%), which was similar to nonapoptotic iRBCs. These findings collectively indicate platelets do not kill bloodstagePlasmodiumat physiologically relevant effector-to-target ratios.P chabaudiprimary and secondary parasitemia was similar in mice depleted of platelets by mAb-injection just before infection, indicating that activation of the protective immune response does not require platelets. In contrast to the lack of an effect on parasite replication, adoptive transfer of WT platelets to CD40-KO mice, which are resistant to experimental cerebral malaria, partially restored experimental cerebral malaria mortality and symptoms in CD40-KO recipients, indicating platelets elicit pathogenesis and platelet CD40 is a key molecule.
authors.affiliation: La Jolla Infectious Disease Institute, San Diego, CA.
authors.forename: Irene
authors.initials: I
authors.lastname: Gramaglia
authors.affiliation: La Jolla Infectious Disease Institute, San Diego, CA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Velez
authors.affiliation: La Jolla Infectious Disease Institute, San Diego, CA.|School of Life Sciences, University of Technology Sydney, Sydney, Australia.
authors.forename: Valery
authors.initials: V
authors.lastname: Combes
authors.affiliation: La Jolla Infectious Disease Institute, San Diego, CA.|Vascular Immunology Unit, University of Sydney, Sydney, Australia; and.
authors.forename: Georges E R
authors.initials: GE
authors.lastname: Grau
authors.affiliation: University of California San Diego, San Diego, CA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wree
authors.affiliation: La Jolla Infectious Disease Institute, San Diego, CA.
authors.forename: Henri C
authors.initials: HC
authors.lastname: van der Heyde
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000469:parasitology / Q000502:physiology*; D019013:CD40 Antigens; D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007111:Immunity, Cellular; D008288:Malaria / Q000097:blood / Q000276:immunology*; D016779:Malaria, Cerebral / Q000209:etiology; D051379:Mice; D016788:Plasmodium chabaudi
chemical_list: D019013:CD40 Antigens