Cell-autonomous targeting of arabinogalactan by host immune factors inhibits 
mycobacterial growth

Qin, L.; Xu, J.; Chen, J.; Wang, S.; Zheng, R.; Cui, Z.; Liu, Z.; Wu, X.; Wang, J.; Huang, X.; Wang, Z.; Wang, M.; Pan, R.; Kaufmann, S. H. E.; Meng, X.; Zhang, L.; Sha, W.; Liu, H.

doi:10.7554/eLife.92737

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Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth

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Kaufmann, S. H. E.
Emeritus Group Systems Immunology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Citation

Qin, L., Xu, J., Chen, J., Wang, S., Zheng, R., Cui, Z., et al. (2024). Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth. eLife, 13: RP92737. doi:10.7554/eLife.92737.

Cite as: https://hdl.handle.net/21.11116/0000-0010-4374-0

Abstract

Deeper understanding of the crosstalk between host cells and Mycobacterium tuberculosis (Mtb) provides crucial guidelines for the rational design of novel intervention strategies against tuberculosis (TB). Mycobacteria possess a unique complex cell wall with arabinogalactan (AG) as a critical component. AG has been identified as a virulence factor of Mtb which is recognized by host galectin-9. Here, we demonstrate that galectin-9 directly inhibited mycobacterial growth through AG-binding property of carbohydrate-recognition domain 2. Furthermore, IgG antibodies with AG specificity were detected in the serum of TB patients. Based on the interaction between galectin-9 and AG, we developed a monoclonal antibody (mAb) screening assay and identified AG-specific mAbs which profoundly inhibit Mtb growth. Mechanistically, proteomic profiling and morphological characterizations revealed that AG-specific mAbs regulate AG biosynthesis, thereby inducing cell wall swelling. Thus, direct AG-binding by galectin-9 or antibodies contributes to protection against TB. Our findings pave the way for the rational design of novel immunotherapeutic strategies for TB control.