Mycobacterial lipomannan induces MAP kinase phosphatase-1 expression in macrophages

Abstract 

Mycobacterial lipomannan (LM) and lipoarabinomannan (LAM) regulate macrophage activation by interacting with Toll-like receptors (TLRs). The intracellular signalling pathways elicited by these complex molecules are poorly defined. We have demonstrated that LM purified from various mycobacterial species, but not LAM from Mycobacterium kansasii or Mycobacterium bovis BCG, induced expression of the MAP kinase phosphatase 1 (MKP-1) in macrophages. Anti-TLR2 antibodies, as well as specific ERK and p38 MAPK inhibitors, decreased MKP-1 transcription in LM-stimulated cells. These findings suggest that the binding of LM to TLR2 triggers MAPK activation, followed by an up-regulation of MKP-1 expression, which in turn may act as a negative regulator of MAPK activation.

Abbreviations: LM, lipomannan, LAM, lipoarabinomannan, MKP-1, MAP kinase phosphatase 1, TLR, Toll-like receptor, MAPK, mitogen activated protein kinases, DC-SIGN, dendritic cell-specific ICAM-3 grabbing non-integrin, ManLAM, mannose-capped lipoarabinomann, PILAM, phosphoinositol-capped lipoarabinomannan

Keywords: Lipomannan, Lipoarabinomannan, Mycobacteria, MAPK, MAP kinase phosphatase-1, Toll-like receptor