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© 2023, Maio et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

During tuberculosis (TB), migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid development of protective T-cell-mediated immunity. However, the mechanisms involved in the delayed migration of DCs during TB are still poorly defined. Here, we found that infection of DCs with Mycobacterium tuberculosis (Mtb) triggers HIF1A-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the lactate dehydrogenase inhibitor oxamate and the HIF1A inhibitor PX-478 abrogated Mtb-induced DC migration in vitro to the lymphoid tissue-specific chemokine CCL21, and in vivo to lymph nodes in mice. Strikingly, we found that although monocytes from TB patients are inherently biased toward glycolysis metabolism, they differentiate into poorly glycolytic and poorly migratory DCs compared with healthy subjects. Taken together, these data suggest that because of their preexisting glycolytic state, circulating monocytes from TB patients are refractory to differentiation into migratory DCs, which may explain the delayed migration of these cells during the disease and opens avenues for host-directed therapies for TB.

Details

Title
Elevated glycolytic metabolism of monocytes limits the generation of HIF1A-driven migratory dendritic cells in tuberculosis
Author
Maio Mariano; Barros Joaquina; Joly Marine; Vahlas Zoi; Marín Franco José Luis; Genoula Melanie; Monard, Sarah C; Vecchione, María Belén; Fuentes, Federico; Gonzalez, Polo Virginia; Quiroga, María Florencia; Vermeulen Mónica; Vu Manh Thien-Phong; Argüello, Rafael J; Inwentarz Sandra; Musella Rosa; Ciallella Lorena; González Montaner Pablo; Palmero Domingo; Lugo Villarino Geanncarlo; Sasiain María del Carmen; Neyrolles Olivier; Vérollet Christel; Balboa Luciana
University/institution
U.S. National Institutes of Health/National Library of Medicine
Publication year
2024
Publication date
2024
Publisher
eLife Sciences Publications Ltd.
e-ISSN
2050084X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3073877846
Copyright
© 2023, Maio et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.