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A systematic analysis of the human immune response to Plasmodium vivax.
Bach, Florian A; Muñoz Sandoval, Diana; Mazurczyk, Michalina; Themistocleous, Yrene; Rawlinson, Thomas A; Harding, Adam C; Kemp, Alison; Silk, Sarah E; Barrett, Jordan R; Edwards, Nick J; Ivens, Alasdair; Rayner, Julian C; Minassian, Angela M; Napolitani, Giorgio; Draper, Simon J; Spence, Philip J.
Afiliação
  • Bach FA; Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
  • Muñoz Sandoval D; Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
  • Mazurczyk M; Insitute of Microbiology, Universidad San Francisco de Quito, Quito, Ecuador.
  • Themistocleous Y; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, and.
  • Rawlinson TA; The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  • Harding AC; The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  • Kemp A; Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
  • Silk SE; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
  • Barrett JR; The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  • Edwards NJ; Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
  • Ivens A; The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  • Rayner JC; Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
  • Minassian AM; The Jenner Institute, University of Oxford, Oxford, United Kingdom.
  • Napolitani G; Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
  • Draper SJ; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
  • Spence PJ; The Jenner Institute, University of Oxford, Oxford, United Kingdom.
J Clin Invest ; 133(20)2023 10 16.
Article em En | MEDLINE | ID: mdl-37616070
BACKGROUNDThe biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate of P. vivax and tracked their response through infection and convalescence.METHODSParticipants were injected intravenously with blood-stage parasites and infection dynamics were tracked in real time by quantitative PCR. Whole blood samples were used for high dimensional protein analysis, RNA sequencing, and cytometry by time of flight, and temporal changes in the host response to P. vivax were quantified by linear regression. Comparative analyses with P. falciparum were then undertaken using analogous data sets derived from prior controlled human malaria infection studies.RESULTSP. vivax rapidly induced a type I inflammatory response that coincided with hallmark features of clinical malaria. This acute-phase response shared remarkable overlap with that induced by P. falciparum but was significantly elevated (at RNA and protein levels), leading to an increased incidence of pyrexia. In contrast, T cell activation and terminal differentiation were significantly increased in volunteers infected with P. falciparum. Heterogeneous CD4+ T cells were found to dominate this adaptive response and phenotypic analysis revealed unexpected features normally associated with cytotoxicity and autoinflammatory disease.CONCLUSIONP. vivax triggers increased systemic interferon signaling (cf P. falciparum), which likely explains its reduced pyrogenic threshold. In contrast, P. falciparum drives T cell activation far in excess of P. vivax, which may partially explain why falciparum malaria more frequently causes severe disease.TRIAL REGISTRATIONClinicalTrials.gov NCT03797989.FUNDINGThe European Union's Horizon 2020 Research and Innovation programme, the Wellcome Trust, and the Royal Society.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Malária Vivax / Malária Falciparum / Malária Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Malária Vivax / Malária Falciparum / Malária Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article