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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection
Nature Medicine, Volume 19, No. 6, Year 2013
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Description
Innate sensing mechanisms trigger a variety of humoral and cellular events that are essential to adaptive immune responses. Here we describe an innate sensing pathway triggered by Plasmodium infection that regulates dendritic cell homeostasis and adaptive immunity through Flt3 ligand (Flt3l) release. Plasmodium-induced Flt3l release in mice requires Toll-like receptor (TLR) activation and type I interferon (IFN) production. We found that type I IFN supports the upregulation of xanthine dehydrogenase, which metabolizes the xanthine accumulating in infected erythrocytes to uric acid. Uric acid crystals trigger mast cells to release soluble Flt3l from a pre-synthesized membrane-associated precursor. During infection, Flt3l preferentially stimulates expansion of the CD8-α+ dendritic cell subset or its BDCA3+ human dendritic cell equivalent and has a substantial impact on the magnitude of T cell activation, mostly in the CD8+ compartment. Our findings highlight a new mechanism that regulates dendritic cell homeostasis and T cell responses to infection. © 2013 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Guermonprez, Pierre
United States, New York
Rockefeller University
Helft, Julie
United States, New York
Icahn School of Medicine at Mount Sinai
Claser, Carla
Singapore, Singapore City
A-star, Singapore Immunology Network
Deroubaix, Stephanie
United States, New York
Rockefeller University
Karanje, Henry
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Gazumyan, Anna
United States, New York
Rockefeller University
Darasse-Jèze, Guillaume
United States, New York
Rockefeller University
Telerman, Stephanie B.
United States, New York
Rockefeller University
Breton, Gaëlle
United States, New York
Rockefeller University
Schreiber, Heidi A.
United States, New York
Rockefeller University
Frias-Staheli, Natalia
United States, New York
Rockefeller University
Billerbeck, Eva
United States, New York
Rockefeller University
Dorner, Marcus
United States, New York
Rockefeller University
Rice, Charles M.
United States, New York
Rockefeller University
Ploss, Alexander
United States, New York
Rockefeller University
Klein, Florian
United States, New York
Rockefeller University
Swiecki, Melissa
United States, St. Louis
Washington University School of Medicine in St. Louis
Colonna, Marco
United States, St. Louis
Washington University School of Medicine in St. Louis
Kamphorst, Alice O.
United States, New York
Rockefeller University
Meredith, Matthew
United States, New York
Rockefeller University
Niec, Rachel
United States, New York
Rockefeller University
Takacs, Constantin
United States, New York
Rockefeller University
Mikhail, Fadi
United States, New York
Weill Cornell Medicine
Hari, Aswin
Canada, Calgary
University of Calgary
Bosque, David
United States, New York
Rockefeller University
Eisenreich, Tom
United States, New York
Rockefeller University
United States, Chevy Chase
Howard Hughes Medical Institute
Merad, Miriam
United States, New York
Icahn School of Medicine at Mount Sinai
Shi, Yan
Canada, Calgary
University of Calgary
Ginhoux, Florent
Singapore, Singapore City
A-star, Singapore Immunology Network
RENIA, LAURENT
Singapore, Singapore City
A-star, Singapore Immunology Network
Urban, Britta Christina
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Nussenzweig, Michel C.
United States, New York
Rockefeller University
United States, Chevy Chase
Howard Hughes Medical Institute
Statistics
Citations: 138
Authors: 32
Affiliations: 9
Identifiers
Doi:
10.1038/nm.3197
ISSN:
10788956
e-ISSN:
1546170X