Poster Presentation First Malaria World Congress 2018

Platelets kill all major Plasmodium species in human malaria (#320)

Steven Kho 1 , Bridget E Barber 1 2 , Edison Johar 3 , Benediktus Andries 4 , Jeanne R Poespoprodjo 4 5 6 , Enny Kenangalem 4 5 , Kim A Piera 1 , Anna Ehmann 3 , Ric N Price 1 7 , Timothy William 2 8 9 , Tonia Woodberry 1 , Simon Foote 3 , Gabriela Minigo 1 , Tsin W Yeo 1 , Matthew J Grigg 1 , Nick M Anstey 1 , Brendan J McMorran 3
  1. Menzies School of Health Research, Tiwi, NT, Australia
  2. Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia
  3. Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, Canberra, ACT, Australia
  4. Timika Malaria Research Program, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia
  5. Rumah Sakit Umum Daerah Kabupaten Mimika, Timika, Papua, Indonesia
  6. Department of Pediatrics, University of Gadjah Mada, Yogyakarta, Indonesia
  7. Nuffield Department of Medicine, University of Oxford, London, United Kingdom
  8. Jesselton Medical Centre, Kota Kinabalu, Sabah, Malaysia
  9. Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

Platelets elicit important functions in the innate immune response, including pathogen killing and host-protection, although the role of platelets in parasite killing in human malaria is unknown. We characterized cell-to-cell platelet interactions by flow cytometry and microscopy in patients naturally infected with P. falciparum, P. vivax, P. malariae or P. knowlesi, from two separate populations in malaria-endemic Indonesia and Malaysia. Our results indicate that platelets interact directly with and kill parasites of all the major Plasmodium species, particularly mature stages. Platelet-mediated killing was greatest in P. vivax. Platelet binding, killing and activation correlated inversely with parasitemia, with platelets likely controlling the growth of a substantial proportion of circulating parasites. We extend in vitro data on PF4-mediated parasite-killing to a second culturable species, P. knowlesi. Platelet-erythrocyte complexes comprised a substantial proportion of the total platelet pool in malaria and may also contribute to malarial thrombocytopenia. Our results indicate that platelets contribute substantially to innate control of Plasmodium infection, and support the design of PF4-based peptides for the species-transcending treatment of malaria.