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Dendritic cells (DCs) are crucial for effective antigen presentation and T\u2010cell activation. In this study, we show that the mycobacterial protein ESAT\u20106 impairs monocyte to DC differentiation, with reduced expression of the DC markers CD209 and CD1a. ESAT\u20106 treatment elevated IL\u20106 and IL\u201010 levels, but blocking the biological activity of these cytokines failed to restore DC differentiation. Mechanistically, ESAT\u20106 suppressed phosphorylation of p65, establishing that ESAT\u20106 impairs DC differentiation by inhibiting NF\u2010\u03baB activation, a function dependent on the last six amino acids of its C\u2010terminal domain. This mechanism may represent a novel immune evasion strategy employed by Mtb to subvert host adaptive immune responses during infection.\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70294","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T12:00:10Z","timestamp":1770120010000},"page":"680-692","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <i>Mycobacterium tuberculosis<\/i>\n                    <scp>ESAT<\/scp>\n                    \u20106 protein inhibits differentiation of human monocytes to dendritic cells"],"prefix":"10.1002","volume":"600","author":[{"given":"Akshay Girish","family":"Manikoth","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Cell Biology BRIC\u2010Centre for DNA Fingerprinting and Diagnostics (CDFD)  Hyderabad India"},{"name":"Graduate Studies Manipal Academy of Higher Education  Manipal 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