Immune Netw.  2019 Apr;19(2):e13. 10.4110/in.2019.19.e13.

Mycobacterium tuberculosis ESAT6 Drives the Activation and Maturation of Bone Marrow-Derived Dendritic Cells via TLR4-Mediated Signaling

• Jang AR
• Kim G
• Hong JJ
• Kang SM
• Shin SJ
• Park JH

• KMID: 2444161
• DOI: http://doi.org/10.4110/in.2019.19.e13

Abstract

6-kDa early secretory antigenic target (ESAT6), a virulent factor of Mycobacterium tuberculosis, is involved in immune regulation. However, the underlying mechanism behind the activation and maturation of dendritic cells (DCs) by ESAT6 remains unclear. In this study, we investigated the effect on TLRs signaling on the regulation of ESAT6-induced activation and maturation of DCs. ESAT6 induced production of IL-6, TNF-α, and IL-12p40 in bone marrow-derived dendritic cells (BMDCs) from wild-type and TLR2-deficient mice, with this induction abolished in TLR4-deficient cells. NF-κB is essential for the ESAT6-induced production of the cytokines in BMDCs. TLR4 was also required for ESAT6-induced activation of NF-κB and MAPKs in BMDCs. ESAT6 additionally upregulated the expression of surface molecules CD80, CD86, and MHC-II, and also promoted the ability of CD4⁺ T cells to secrete IFN-γ via the TLR4-dependent pathway. Our findings suggest that TLR4 is critical in the activation and maturation of DCs in response to ESAT6.

Keyword

Mycobacterium tuberculosis; ESAT6 protein; TLR4 receptor; Dendritic cells

MeSH Terms

Animals
Cytokines
Dendritic Cells*
Interleukin-12 Subunit p40
Interleukin-6
Mice
Mycobacterium tuberculosis*
Mycobacterium*
T-Lymphocytes
Toll-Like Receptor 4
Cytokines
Interleukin-12 Subunit p40
Interleukin-6
Toll-Like Receptor 4