[Mannose-capped lipoarabinomannan (ManLAM) binding TLR2 activates mast cells to release exosomes and induces M2 polarization of macrophages].

Objective To explore the mechanism of mannose-capped lipoarabinomannan (ManLAM) lipopolysaccharide of mycobacterium tuberculosis (MTB) inducing exosomes of mast cells to recruit macrophages and influence macrophage polarization for immune evasion. Methods H37Rv MTB was cultured and ManLAM extracted and identified. The extracted ManLAM was used to treat mast cells, and the exosomes secreted by mast cells were collected. The protein components of the exosomes were analyzed and identified by proteomic analysis and Western blotting. The collected exosomes were co-cultured with macrophages differentiated from THP-1 cells. The chemotaxis of exosomes released by mast cells on macrophages was detected by Transwell assay. The macrophage polarization induced by ManLAM was detected by flow cytometry and real-time quantitative PCR. Results ManLAM was successfully extracted and purified, and the ratio of mannose to arabinose was about 12.6:9.4 identified by gas chromatography. ManLAM bound to Toll-like receptor 2 of mast cells, the exosomes produced by those mast cells had a high levels of CCL2, IL-4, and IL-13. ManLAM-induced mast cell exosomes recruited macrophages and promoted high expression of M2 polarization of macrophages molecular markers: arginase-1, IL-10, and FIZZ-1. Conclusions ManLAM stimulates mast cells to secrete exosomes and indirectly induces M2 polarization of macrophages, which makes MTB evade immune clearance.