Phylactic role of anti-lipoarabinomannan IgM directed against mannan core during mycobacterial infection in macrophages
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
Mycobacteria enter host phagocytes, such as macrophages by binding to several receptors on phagocytes. Several mycobacterial species, including Mycobacterium tuberculosis have evolved systems to evade host bactericidal pathways. Lipoarabinomannan (LAM) is an essential mycobacterial molecule for both binding to phagocytes and escaping from bactericidal pathways. Integrin CD11b plays critical roles as a phagocytic receptor and contributes to host defense by mediating both nonopsonic and opsonic phagocytosis. However, the mechanisms by which CD11b-mediated phagocytosis associates with LAM and drives the phagocytic process of mycobacteria remain to be fully elucidated. We recently identified TMDU3 as anti-LAM IgM antibody against the mannan core of LAM. The present study investigated the roles of CD11b and TMDU3 in macrophage phagocytosis of mycobacteria and subsequent bactericidal lysosomal fusion to phagosomes. CD11b knockout cells generated by a CRISPR/Cas9 system showed significant attenuation of the ability to phagocytose non-opsonized mycobacteria and LAM-conjugated beads. Moreover, recombinant human CD11b protein was found to bind to LAM. TMDU3 markedly inhibited macrophage phagocytosis of non-opsonized mycobacteria. This antibody slightly increased the phagocytosis of mycobacteria under opsonized conditions, whereas it significantly enhanced CD11b-mediated bactericidal functions. Taken together, these results show a novel phylactic role of anti-LAM IgM during mycobacterial infection in macrophages.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:143 |
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| Enthalten in: |
Tuberculosis (Edinburgh, Scotland) - 143(2023) vom: 27. Dez., Seite 102391 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nakayama, Hitoshi [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-LAM IgM |
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| Anmerkungen: |
Date Completed 04.12.2023 Date Revised 28.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.tube.2023.102391 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Mycobacteria enter host phagocytes, such as macrophages by binding to several receptors on phagocytes. Several mycobacterial species, including Mycobacterium tuberculosis have evolved systems to evade host bactericidal pathways. Lipoarabinomannan (LAM) is an essential mycobacterial molecule for both binding to phagocytes and escaping from bactericidal pathways. Integrin CD11b plays critical roles as a phagocytic receptor and contributes to host defense by mediating both nonopsonic and opsonic phagocytosis. However, the mechanisms by which CD11b-mediated phagocytosis associates with LAM and drives the phagocytic process of mycobacteria remain to be fully elucidated. We recently identified TMDU3 as anti-LAM IgM antibody against the mannan core of LAM. The present study investigated the roles of CD11b and TMDU3 in macrophage phagocytosis of mycobacteria and subsequent bactericidal lysosomal fusion to phagosomes. CD11b knockout cells generated by a CRISPR/Cas9 system showed significant attenuation of the ability to phagocytose non-opsonized mycobacteria and LAM-conjugated beads. Moreover, recombinant human CD11b protein was found to bind to LAM. TMDU3 markedly inhibited macrophage phagocytosis of non-opsonized mycobacteria. This antibody slightly increased the phagocytosis of mycobacteria under opsonized conditions, whereas it significantly enhanced CD11b-mediated bactericidal functions. Taken together, these results show a novel phylactic role of anti-LAM IgM during mycobacterial infection in macrophages | ||
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| 700 | 1 | |a Takamori, Kenji |e verfasserin |4 aut | |
| 700 | 1 | |a Ogawa, Hideoki |e verfasserin |4 aut | |
| 700 | 1 | |a Iwabuchi, Kazuhisa |e verfasserin |4 aut | |
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