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Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth
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Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth
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Journal Article
Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth
2024
Overview
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.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
/ Antibodies, Monoclonal - immunology
/ antibody
/ Antigens
/ Bacteria
/ BCG
/ E coli
/ Female
/ Growth
/ Host-Pathogen Interactions - immunology
/ Humans
/ Immunologic Factors - metabolism
/ Immunologic Factors - pharmacology
/ Mice
/ Microbiology and Infectious Disease
/ Mycobacterium tuberculosis - growth & development
/ Mycobacterium tuberculosis - immunology
