Mycobacterium tuberculosis (Mtb) induces maturation of Monocytes-derived Dendritic Cells (M-DC) involving TLR2 and DC-SIGN receptors.

ALEMÁN M; DE LA BARRERA S; SCHIERLOH P; YOKOBORI N; ALVES L; ABBATE E; SASIAIN MC

Córdoba. Argentina

Congreso; VII Latin American Congress of Immunology; 2005

Asociación Latinoamericana de Inmunología (ALAI)

Mtb treated M-DC display a phenotype consistent with that of a mature DC. The aim of this study was to investigate the pathways involved in Mtb induced M-DC maturation process. Peripheral monocytes were cultured in RPMI 10% FCS with IL-4 and GM-CSF at 37oC in 5% CO2. On day 5 cells were 70-80% CD1a+ and 95% CD14- and the maturation was achieved by treatment with Mtb, LAM,or LPS for 24 h in the presence of not of MAPK inhibitors (SB,PD), PI3K inhibitor (wortmannin), anti-TLR2 blocking antibody. Results: blockade of TLR2 inhibited Mtb-induced expression of CD86 and IL-12 production: % cells and expression (MFr) of IL-12 (% cells: Mtb=31±2, a-TLR2= 15±7; MFr: Mtb=48±5, a-TLR2= 14±6, p<0.005) and CD86 (% cells: Mtb=59±3, a-TLR2=35±15, MFr: Mtb=22±2, a-TLR2=14±3, p<0.05). IL-12 (% cells: SB=8±3, MFr: SB=10±6, p<0.03) and CD86 (% cells: SB=31±11, MFr: SB=14, p<0.05) were inhibited by SB.  Neither A-TLR2 nor SB affect CD83 MFr. The presence of Mtb down-regulated DC-SIGN  (% cells, control= 86±7, Mtb=46±9,  MF: control=357±31, Mtb=199±28, p<0.01). Mtb induced DC maturation was not interfered by ManLAM suggesting that Mtb induces M-DC maturation via TLR2 signaling pathway and DC-SIGN and not via mannose receptor.