Journal article
Regulatory T cells impede acute and long-term immunity to blood-stage malaria through CTLA-4
Nature medicine, Vol.23(10), pp.1220-1225
10/2017
DOI: 10.1038/nm.4395
PMCID: PMC5649372
PMID: 28892065
Abstract
Malaria, caused by the protozoan Plasmodium, is a devastating mosquito-borne disease with the potential to affect nearly half the world's population. Despite mounting substantial T and B cell responses, humans fail to efficiently control blood-stage malaria or develop sterilizing immunity to reinfections. Although forkhead box P3 (FOXP3)
CD4
regulatory T (T
) cells form a part of these responses, their influence remains disputed and their mode of action is unknown. Here we show that T
cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (T
)-B cell interactions in germinal centers. Mechanistically, T
cells function in a critical temporal window to impede protective immunity through cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Targeting T
cells or CTLA-4 in this precise window accelerated parasite clearance and generated species-transcending immunity to blood-stage malaria in mice. Our study uncovers a critical mechanism of immunosuppression associated with blood-stage malaria that delays parasite clearance and prevents development of potent adaptive immunity to reinfection. These data also reveal a temporally discrete and potentially therapeutically amenable functional role for T
cells and CTLA-4 in limiting antimalarial immunity.
Details
- Title: Subtitle
- Regulatory T cells impede acute and long-term immunity to blood-stage malaria through CTLA-4
- Creators
- Samarchith P Kurup - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USANyamekye Obeng-Adjei - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Rockville, Maryland, USAScott M Anthony - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USABoubacar Traore - Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, MaliOgobara K Doumbo - Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, MaliNoah S Butler - Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAPeter D Crompton - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Rockville, Maryland, USAJohn T Harty - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.23(10), pp.1220-1225
- DOI
- 10.1038/nm.4395
- PMID
- 28892065
- PMCID
- PMC5649372
- NLM abbreviation
- Nat Med
- ISSN
- 1546-170X
- eISSN
- 1546-170X
- Publisher
- United States
- Grant note
- R01 AI095178 / NIAID NIH HHS R01 AI085515 / NIAID NIH HHS R01 AI100527 / NIAID NIH HHS R01 AI127481 / NIAID NIH HHS R01 AI125446 / NIAID NIH HHS P20 GM103447 / NIGMS NIH HHS
- Language
- English
- Date published
- 10/2017
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984001214802771
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