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Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors

Macrophages (MФ), the primary cell of the innate immune system, serves as the first line of defense. During bacterial infection, Gram-negative (G-) bacteria release nanosized outer membrane vesicles (OMVs), facilitating the crosstalk between the microbe and the host. The underlying mechanisms by whi...

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Autores principales: Sivanantham, Ayyanar, Alktaish, Ward, Murugeasan, Selvakumar, Gong, Bin, Lee, Heedoo, Jin, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933776/
https://www.ncbi.nlm.nih.gov/pubmed/36817491
http://dx.doi.org/10.3389/fimmu.2023.1044834
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author Sivanantham, Ayyanar
Alktaish, Ward
Murugeasan, Selvakumar
Gong, Bin
Lee, Heedoo
Jin, Yang
author_facet Sivanantham, Ayyanar
Alktaish, Ward
Murugeasan, Selvakumar
Gong, Bin
Lee, Heedoo
Jin, Yang
author_sort Sivanantham, Ayyanar
collection PubMed
description Macrophages (MФ), the primary cell of the innate immune system, serves as the first line of defense. During bacterial infection, Gram-negative (G-) bacteria release nanosized outer membrane vesicles (OMVs), facilitating the crosstalk between the microbe and the host. The underlying mechanisms by which OMVs induced pro-inflammatory (M1) activation are still unknown. Our study shows that OMVs caused M1 activation via modulating various toll-like receptor (TLR) expressions as they contain LPS, LTA, bacterial DNAs, and flagellins. Also, we found that caveolin-1 (cav-1), a 21-kDa scaffolding protein of caveolae and lipid rafts, plays a significant role in OMV-induced pro-inflammatory response in regulating various TLR signaling pathways. Specifically, cav-1 deletion increased the expression of OMV-induced TLRs, pro-inflammatory cytokine secretions (TNF-α and IL-1β), and the reactive oxygen species (ROS) production in MФs. Further, we examined the interaction between Cav-1 and TLR4 by immunoprecipitation, colocalization, and computational models, providing future direction to explore the role of cav-1 in OMV-induced other TLR signaling. Altogether, Cav-1 is a key regulator in OMV-induced multiple TLRs response. This study promotes future research to develop drugs by targeting the specific motif of cav-1 or TLRs against bacterial infection and macrophage-mediated inflammation.
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spelling pubmed-99337762023-02-17 Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors Sivanantham, Ayyanar Alktaish, Ward Murugeasan, Selvakumar Gong, Bin Lee, Heedoo Jin, Yang Front Immunol Immunology Macrophages (MФ), the primary cell of the innate immune system, serves as the first line of defense. During bacterial infection, Gram-negative (G-) bacteria release nanosized outer membrane vesicles (OMVs), facilitating the crosstalk between the microbe and the host. The underlying mechanisms by which OMVs induced pro-inflammatory (M1) activation are still unknown. Our study shows that OMVs caused M1 activation via modulating various toll-like receptor (TLR) expressions as they contain LPS, LTA, bacterial DNAs, and flagellins. Also, we found that caveolin-1 (cav-1), a 21-kDa scaffolding protein of caveolae and lipid rafts, plays a significant role in OMV-induced pro-inflammatory response in regulating various TLR signaling pathways. Specifically, cav-1 deletion increased the expression of OMV-induced TLRs, pro-inflammatory cytokine secretions (TNF-α and IL-1β), and the reactive oxygen species (ROS) production in MФs. Further, we examined the interaction between Cav-1 and TLR4 by immunoprecipitation, colocalization, and computational models, providing future direction to explore the role of cav-1 in OMV-induced other TLR signaling. Altogether, Cav-1 is a key regulator in OMV-induced multiple TLRs response. This study promotes future research to develop drugs by targeting the specific motif of cav-1 or TLRs against bacterial infection and macrophage-mediated inflammation. Frontiers Media S.A. 2023-02-02 /pmc/articles/PMC9933776/ /pubmed/36817491 http://dx.doi.org/10.3389/fimmu.2023.1044834 Text en Copyright © 2023 Sivanantham, Alktaish, Murugeasan, Gong, Lee and Jin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Sivanantham, Ayyanar
Alktaish, Ward
Murugeasan, Selvakumar
Gong, Bin
Lee, Heedoo
Jin, Yang
Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors
title Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors
title_full Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors
title_fullStr Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors
title_full_unstemmed Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors
title_short Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors
title_sort caveolin-1 regulates omv-induced macrophage pro-inflammatory activation and multiple toll-like receptors
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933776/
https://www.ncbi.nlm.nih.gov/pubmed/36817491
http://dx.doi.org/10.3389/fimmu.2023.1044834
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