Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth
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.
Authors
- Mingqiao Wang (ORCID: https://orcid.org/0000-0003-0439-007X)
- Stefan H. E. Kaufmann (ORCID: https://orcid.org/0000-0001-9866-8268)
- Zhenling Cui (ORCID: https://orcid.org/0000-0002-5419-3771)
- Lianhua Qin (ORCID: https://orcid.org/0000-0001-9894-4170)
- Ruijuan Zheng
- Xiaochen Huang (ORCID: https://orcid.org/0000-0001-7626-1803)
- Sen Wang (ORCID: https://orcid.org/0000-0001-7179-626X)
- Zhaohui Wang (ORCID: https://orcid.org/0000-0001-7994-7464)
- Lu Zhang (ORCID: https://orcid.org/0000-0002-3195-4291)
- Zhonghua Liu (ORCID: https://orcid.org/0000-0001-9689-7753)
- Jie Wang (ORCID: https://orcid.org/0000-0002-1659-0637)
- Xun Meng (ORCID: https://orcid.org/0009-0004-5243-2419)
- Haipeng Liu (ORCID: https://orcid.org/0000-0002-3338-6291)
- Wei Sha (ORCID: https://orcid.org/0000-0002-2099-8205)
- Junfang Xu (ORCID: https://orcid.org/0000-0002-4150-7305)
- Jianxia Chen (ORCID: https://orcid.org/0009-0000-7548-7261)
- Rong Pan
- X. Wu (ORCID: https://orcid.org/0000-0002-8943-8054)
Institutions
- Tongji University (CN)
- Walmart (United States) (US)
- Fudan University (CN)
- Institute for Advanced Study (US)
- Max Planck Institute for Infection Biology (DE)
- e-Therapeutics (United Kingdom) (GB)
- National Clinical Research (US)
- Shanghai Pulmonary Hospital (CN)
- Huashan Hospital (CN)
- Max Planck Institute for Multidisciplinary Sciences (DE)
Publication Details
- Journal
- eLife
- Published
- 2024-11-04
- DOI
- https://doi.org/10.7554/elife.92737.3
- Primary Topic
- Galectins and Cancer Biology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality
- Tongji University
- Young Scientists Fund
- Shanghai Shuguang Program