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Sensing of mycobacterial arabinogalactan by galectin‐9 exacerbates mycobacterial infection
- Source :
- EMBO Reports
- Publication Year :
- 2021
- Publisher :
- EMBO, 2021.
-
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.<br />Arabinogalactan is a virulence factor of mycobacteria. Binding of galectin‐9 to mycobacterial arabinogalactan triggers matrix metalloproteinases via TAK1‐ERK signaling, which promotes mycobacterial infection and increases lung injury.
- Subjects :
- Galectins
galectin‐9
virulence factor
Galactans
Biochemistry
Article
Virulence factor
Microbiology
Mycobacterium tuberculosis
Mice
03 medical and health sciences
0302 clinical medicine
Arabinogalactan
Genetics
Animals
Molecular Biology
Zebrafish
030304 developmental biology
Galectin
0303 health sciences
Mycobacterium bovis
mycobacterial arabinogalactan
biology
Kinase
Chemistry
matrix metalloproteinases
transforming growth factor β‐activated kinase 1
Articles
biology.organism_classification
Microbiology, Virology & Host Pathogen Interaction
030217 neurology & neurosurgery
Signal Transduction
Transforming growth factor
Mycobacterium
Subjects
Details
- ISSN :
- 14693178 and 1469221X
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- EMBO reports
- Accession number :
- edsair.doi.dedup.....a8aa5cc6dd549fa72e4034e6d72f120b