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bioRxiv · 10.1101/2025.08.06.668872

ESAT-6 protein of Mycobacterium tuberculosis inhibits differentiation of human monocytes to dendritic cells

Manikoth, A. G.·Qureshi, R.·Mukhopadhyay, S.
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Abstract

Mycobacterium tuberculosis (Mtb) employs multiple strategies to evade host immunity, including disruption of antigen presentation. Dendritic cells (DCs) are crucial for effective antigen presentation and T-cell activation. In this study, we show that mycobacterial protein, ESAT-6, impairs monocyte to DC differentiation with reduced expression of the DC marker, CD209. ESAT-6 treatment elevated IL-6 and IL-10 levels, but blocking of these cytokines failed to restore DC differentiation. Mechanistically, ESAT-6 suppressed phosphorylation of p65, establishing that ESAT-6 impairs DC differentiation by inhibiting NF-{kappa}B activation and this function is dependent on the last six amino acids of its C-terminal domain. This mechanism may represent a novel immune evasion strategy employed by Mtb to subvert host adaptive immune responses during infection.

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Manikoth, A. G., Qureshi, R., Mukhopadhyay, S.. 2025-08-08. ESAT-6 protein of Mycobacterium tuberculosis inhibits differentiation of human monocytes to dendritic cells. https://doi.org/10.1101/2025.08.06.668872

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