PUBLICATION
Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection
- Authors
- Wu, X., Wu, Y., Zheng, R., Tang, F., Qin, L., Lai, D., Zhang, L., Chen, L., Yan, B., Yang, H., Wang, Y., Li, F., Zhang, J., Wang, F., Wang, L., Cao, Y., Ma, M., Liu, Z., Chen, J., Huang, X., Wang, J., Jin, R., Wang, P., Sun, Q., Sha, W., Lyu, L., Moura-Alves, P., Dorhoi, A., Pei, G., Zhang, P., Chen, J., Gao, S., Randow, F., Zeng, G., Chen, C., Ye, X.S., Kaufmann, S.H.E., Liu, H., Ge, B.
- ID
- ZDB-PUB-210515-14
- Date
- 2021
- Source
- EMBO reports 22(7): e51678 (Journal)
- Registered Authors
- Keywords
- galectin-9, matrix metalloproteinases, mycobacterial arabinogalactan, transforming growth factor β-activated kinase 1, virulence factor
- MeSH Terms
-
- Animals
- Galactans
- Galectins/genetics
- Mice
- Mycobacterium tuberculosis*
- Zebrafish*
- PubMed
- 33987949 Full text @ EMBO Rep.
Citation
Wu, X., Wu, Y., Zheng, R., Tang, F., Qin, L., Lai, D., Zhang, L., Chen, L., Yan, B., Yang, H., Wang, Y., Li, F., Zhang, J., Wang, F., Wang, L., Cao, Y., Ma, M., Liu, Z., Chen, J., Huang, X., Wang, J., Jin, R., Wang, P., Sun, Q., Sha, W., Lyu, L., Moura-Alves, P., Dorhoi, A., Pei, G., Zhang, P., Chen, J., Gao, S., Randow, F., Zeng, G., Chen, C., Ye, X.S., Kaufmann, S.H.E., Liu, H., Ge, B. (2021) Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection. EMBO reports. 22(7):e51678.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping