
Mycobacterium tuberculosis infection triggers a glycolytic metabolic profile in dendritic cells, which is essential for their migration to lymph nodes. However, the glycolytic state of monocytes from tuberculosis patients impairs the ability of derived dendritic cells to migrate in response to Mycobacterium tuberculosis.


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During tuberculosis, 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 triggers HIF-1α-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the glycolysis inhibitor oxamate and the HIF-1α inhibitor PX-478 abrogated M. tuberculosis -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.

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### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

Elevated glycolytic metabolism of monocytes limits the generation of HIF-1α-driven migratory dendritic cells in tuberculosis

mycobacterium-tuberculosis-infection-impairs-dendritic-cell-migration-by-disrupting-glycolytic-metabolism


Mycobacterium tuberculosis Infection Impairs Dendritic Cell Migration by Disrupting Glycolytic Metabolism
