Journal article
Transcriptional profiling and immunophenotyping show sustained activation of blood monocytes in subpatentPlasmodium falciparuminfection
Jessica R Loughland, Tonia Woodberry, Matt Field, Dean W Andrew, Arya SheelaNair, Nicholas L Dooley, Kim A Piera, Fiona H Amante, Enny Kenangalem, Ric N Price, Christian R Engwerda, Nicholas M Anstey, James S McCarthy, Michelle J Boyle, Gabriela Minigo
Clinical & Translational Immunology | Wiley Open Access | Published : 2020
DOI: 10.1002/cti2.1144
Abstract
Objectives Malaria, caused by Plasmodium infection, remains a major global health problem. Monocytes are integral to the immune response, yet their transcriptional and functional responses in primary Plasmodium falciparum infection and in clinical malaria are poorly understood. Methods The transcriptional and functional profiles of monocytes were examined in controlled human malaria infection with P. falciparum blood stages and in children and adults with acute malaria. Monocyte gene expression and functional phenotypes were examined by RNA sequencing and flow cytometry at peak infection and compared to pre-infection or at convalescence in acute malaria. Results In subpatent primary infect..
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Grants
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by Channel 7 Children's Research Foundation
Awarded by Wellcome Trust
Funding Acknowledgements
We thank the Q-pharm staff who conducted the human blood-stage infection studies and in particular Dr Suzanne Elliot, Nannette Douglas and Gem Mackenroth for supporting the research. We thank Dr Paul Griffin for advice and technical assistance. We thank all staff with the Papuan Community Health and Development Foundation, and all teams involved in the Timika clinical malaria studies. We thank Dr Derek Sarovich for advice on study design and Fabian de Labastida Rivera for laboratory support. We thank the Australian Red Cross Blood Service for their support. We thank the volunteers who participated in all clinical trials and Medicine for Malaria Venture for funding these studies. This work was funded by the National Health and Medical Research Council (NHMRC, Program Grant 1132975 to NMA, JSM, CRE; Program Grants 1037304 and 1092789; Project Grant 1045156; and Senior Principal Research Fellowship 1042072 to NMA, Practitioner Fellowship 1135955 to JSM, Senior Research Fellowship 1154265 to CRE, Project Grant 1125656 and Career Development Award 141632 to MJB, and MF is funded by APP5121190). RP is a Wellcome Trust Senior Fellow in Clinical Science (200909) and Channel 7 Children's Research Foundation (Grant 151016). The clinical trials that enabled sample collection were funded by the Medicines for Malaria Venture. The Timika Malaria Research Program is supported by the Australian Department of Foreign Affairs. The views expressed in this publication are those of the authors and do not reflect the views of the NHMRC. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.