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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection
Nature Immunology, Volume 13, No. 2, Year 2012
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Description
Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4 + T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4 + T cells that determine protection or parasite persistence remain unknown. Here we show that infection of humans with Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD-1 associated with T cell dysfunction. In vivo blockade of the PD-1 ligand PD-L1 and the inhibitory receptor LAG-3 restored CD4 + T cell function, amplified the number of follicular helper T cells and germinal-center B cells and plasmablasts, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, and proper function can be restored by inhibitory therapies to enhance parasite control. © 2012 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Butler, Noah S.
United States, Iowa City
University of Iowa
Moebius, Jacqueline
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Pewe, Lecia L.
United States, Iowa City
University of Iowa
Traoré, Boubacar M.
Mali, Bamako
University of Bamako
Doumbo, Ogobara K.
Mali, Bamako
University of Bamako
Tygrett, Lorraine T.
United States, Iowa City
University of Iowa
Waldschmidt, Thomas J.
United States, Iowa City
University of Iowa
Crompton, Peter Dobbs
United States, Iowa City
University of Iowa
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Harty, John T.
United States, Iowa City
University of Iowa
Statistics
Citations: 268
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.1038/ni.2180
ISSN:
15292908
e-ISSN:
15292916
Research Areas
Infectious Diseases