Mycobacterium tuberculosis lipoarabinomannan enhances LPS-induced TNF-α production and inhibits NO secretion by engaging scavenger receptors

Lipoarabinomannan capped with terminal oligomannosides (ManLAM) is a component of mycobacteria cell wall enabling Mycobacterium tuberculosis to infect macrophages. We found that short treatment (3.5 h) of macrophage-like J774 cells and thioglycollate-elicited peritoneal murine macrophages with ManLAM and its deacylated form enhanced LPS-stimulated release of tumor necrosis factor-alpha (TNF-alpha). In contrast, prolong incubation of J774 cells with ManLAM (16 h) led to inhibition of LPS-stimulated TNF-alpha production. LPS-triggered secretion of nitric oxide (NO) was suppressed by ManIAM and its deacylated form. Effects of ManLAM and its deacylated derivative were mimicked by dextran sulfate, a general ligand of scavenger receptors. The enhancement of LPS-induced TNF-alpha production by dextran sulfate was partially reversed by an antibody neutralizing scavenger receptor SR-PSOX/CXCL16 while the stimulatory activity of deacylated ManLAM was reversed by an antibody neutralizing class B scavenger receptor CD36. Our data suggest that CD36 mediates the activity of ManLAM and its deacylated form leading to TNF-alpha release in LPS-stimulated J774 cells and peritoneal murine macrophages, while NO production is modulated by unknown scavenger receptors. (C) 2011 Elsevier Ltd. All rights reserved.