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Sensing of mycobacterial arabinogalactan by galectin‐9 exacerbates mycobacterial infection
Author(s) -
Wu Xiangyang,
Wu Yong,
Zheng Ruijuan,
Tang Fen,
Qin Lianhua,
Lai Detian,
Zhang Lu,
Chen Lingming,
Yan Bo,
Yang Hua,
Wang Yang,
Li Feifei,
Zhang Jinyu,
Wang Fei,
Wang Lin,
Cao Yajuan,
Ma Mingtong,
Liu Zhonghua,
Chen Jianxia,
Huang Xiaochen,
Wang Jie,
Jin Ruiliang,
Wang Peng,
Sun Qin,
Sha Wei,
Lyu Liangdong,
MouraAlves Pedro,
Dorhoi Anca,
Pei Gang,
Zhang Peng,
Chen Jiayu,
Gao Shaorong,
Randow Felix,
Zeng Gucheng,
Chen Chang,
Ye XinShan,
Kaufmann Stefan H E,
Liu Haipeng,
Ge Baoxue
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202051678
Subject(s) - mycobacterium tuberculosis , microbiology and biotechnology , mycobacterium , biology , virulence factor , galectin 3 , galectin , matrix metalloproteinase , virulence , immune system , mycobacterium bovis , tuberculosis , zebrafish , mycobacterium marinum , immunology , bacteria , medicine , biochemistry , genetics , pathology , gene
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.