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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques
Science Immunology, Volume 6, No. 55, Article eabf3861, Year 2021
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Description
Boosting immune cell function by targeting the coinhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here, we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with anti–PD-1 monoclonal antibody developed worse disease and higher granuloma bacterial loads compared with isotype control–treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in anti–PD-1–treated macaques were not increased in number or function in granulomas, expressed increased levels of CTLA-4, and exhibited reduced intralesional trafficking in live imaging studies. In granulomas of anti–PD-1–treated animals, multiple proinflammatory cytokines were elevated, and more cytokines correlated with bacterial loads, leading to the identification of a role for caspase 1 in the exacerbation of tuberculosis after PD-1 blockade. Last, increased Mtb bacterial loads after PD-1 blockade were found to associate with the composition of the intestinal microbiota before infection in individual macaques. Therefore, PD-1–mediated coinhibition is required for control of Mtb infection in macaques, perhaps because of its role in dampening detrimental inflammation and allowing for normal CD4 T cell responses. Copyright © 2021 The Authors,
Authors & Co-Authors
Kauffman, Keith D.
United States, Bethesda
National Institutes of Health Nih
Sakai, Shunsuke
United States, Bethesda
National Institutes of Health Nih
Lora, Nickiana E.
United States, Bethesda
National Institutes of Health Nih
Namasivayam, Sivaranjani
United States, Bethesda
National Institutes of Health Nih
Baker, Paul J.
United States, Bethesda
National Institutes of Health Nih
Kamenyeva, Olena
United States, Bethesda
National Institutes of Health Nih
Foreman, Taylor W.
United States, Bethesda
National Institutes of Health Nih
Nelson, Christine E.
United States, Bethesda
National Institutes of Health Nih
Oliveira-De-Souza, Deivide
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Vinhaes, Caian Leal
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Sette, Alessandro D.
United States, La Jolla
La Jolla Institute for Immunology
United States, La Jolla
University of California, San Diego
Freeman, Gordon James
United States, Boston
Dana-farber Cancer Institute
Moore, Rashida M.
United States, Bethesda
National Institutes of Health Nih
Sher, Alan F.
United States, Bethesda
National Institutes of Health Nih
Mayer-Barber, Katrin D.
United States, Bethesda
National Institutes of Health Nih
Andrade, Bruno B.
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Kabát, Juraj
United States, Bethesda
National Institutes of Health Nih
Via, L. E.
United States, Bethesda
National Institutes of Health Nih
Barber, Daniel L.
United States, Bethesda
National Institutes of Health Nih
Bleach, Janard L.
Unknown Affiliation
Butler, Ashley L.
Unknown Affiliation
Dayao, Emmanuel K.
Unknown Affiliation
Fleegle, Joel D.
Unknown Affiliation
Gomez, Felipe
Unknown Affiliation
Piazza, Michaela K.
Unknown Affiliation
Repoli, Katelyn M.
Unknown Affiliation
Slone, Becky Y.
Unknown Affiliation
Sutphin, Michelle K.
Unknown Affiliation
Walker, April M.
Unknown Affiliation
Weiner, Danielle M.
Unknown Affiliation
Woodcock, Michael J.
Unknown Affiliation
Statistics
Citations: 51
Authors: 31
Affiliations: 5
Identifiers
Doi:
10.1126/SCIIMMUNOL.ABF3861
ISSN:
24709468