Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection

Journal article

Mycobacterial arabinogalactan (AG) is an essential cell wall component of mycobacteria and a frequent structural and bio-synthetical target for anti-tuberculosis (TB) drug development. Here, we report that mycobacterial AG is recognized by galectin-9 and exacerbates mycobacterial infection. Administration of AG-specific aptamers inhibits cellular infiltration caused by Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG, and moderately increases survival of Mtb-infected mice or Mycobacterium marinum-infected zebrafish. AG interacts with carbohydrate recognition domain (CRD) 2 of galectin-9 with high affinity, and galectin-9 associates with transforming growth factor β-activated kinase 1 (TAK1) via CRD2 to trigger subsequent activation of extracellular signal-regulated kinase (ERK) as well as induction of the expression of matrix metalloproteinases (MMPs). Moreover, deletion of galectin-9 or inhibition of MMPs blocks AG-induced pathological impairments in the lung, and the AG-galectin-9 axis aggravates the process of Mtb infection in mice. These results demonstrate that AG is an important virulence factor of mycobacteria and galectin-9 is a novel receptor for Mtb and other mycobacteria, paving the way for the development of novel effective TB immune modulators.

Authors: Wu, X; Wu, Y; Zheng, R; Tang, F; Qin, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: EMBO Press
• Journal: EMBO Reports
• Volume: 22
• Issue: 7
• Article number: e51678
• Publication date: 2021-05-13
• Acceptance date: 2021-04-16
• DOI: 10.15252/embr.202051678
• EISSN: 1469-3178
• ISSN: 1469-221X
• Language: English
• Keywords: FFR