Transcriptional profiling and immunophenotyping show sustained activation of blood monocytes in subpatent Plasmodium falciparum infection
Year: 2020
Type: article
Study design: Observational Study
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 infection, the monocyte transcriptional profile was dominated by an interferon (IFN) molecular signature. Pathways enriched included type I IFN signalling, innate immune response and cytokine‐mediated signalling. Monocytes increased TNF and IL‐12 production upon in vitro toll‐like receptor stimulation and increased IL‐10 production upon in vitro parasite restimulation. Longitudinal phenotypic analyses revealed sustained significant changes in the composition of monocytes following infection, with increased CD14+CD16− and decreased CD14−CD16+ subsets. In acute malaria, monocyte CD64/FcγRI expression was significantly increased in children and adults, while HLA‐DR remained stable. Although children and adults showed a similar pattern of differentially expressed genes, the number and magnitude of gene expression change were greater in children. Conclusions Monocyte activation during subpatent malaria is driven by an IFN molecular signature with robust activation of genes enriched in pathogen detection, phagocytosis, antimicrobial activity and antigen presentation. The greater magnitude of transcriptional changes in children with acute malaria suggests monocyte phenotypes may change with age or exposure.
DOI: 10.1002/cti2.1144
Institutions: QIMR Berghofer Medical Research Institute, Menzies School of Health Research, Charles Darwin University, Australian National University, Australian Institute of Tropical Health and Medicine, James Cook University, Ministry of Health, Mahidol University, University of Oxford, Mahidol Oxford Tropical Medicine Research Unit
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,200
Awards: G2840046572, Translational Studies in Malaria, G4998995227, Understanding malaria in the human host, Improving the treatment of Plasmodium vivax, T-follicular helper cell subsets that induce protective anti-Plasmodium falciparum antibodies, Tropical diseases: Translating discoveries into better health, G7188662219, Discovering novel immune targets for treating infectious diseases, Tropical Disease - immunity, pathogenesis and vaccine development: global translation, Improving the treatment of Plasmodium vivax, Comparative pathophysiology of severe knowlesi and falciparum malaria, Pathophysiology and treatment of malaria and other tropical infectious diseases prevalent in our region
OpenAlex ID: W3036111225