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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1044834/full |
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| author | Ayyanar Sivanantham Ward Alktaish Selvakumar Murugeasan Bin Gong Heedoo Lee Heedoo Lee Yang Jin |
| author_facet | Ayyanar Sivanantham Ward Alktaish Selvakumar Murugeasan Bin Gong Heedoo Lee Heedoo Lee Yang Jin |
| author_sort | Ayyanar Sivanantham |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-10T18:02:45Z |
| format | Article |
| id | doaj.art-70f748e1759a4467882790683bd347a9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T18:02:45Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-70f748e1759a4467882790683bd347a92023-02-02T14:46:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.10448341044834Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptorsAyyanar Sivanantham0Ward Alktaish1Selvakumar Murugeasan2Bin Gong3Heedoo Lee4Heedoo Lee5Yang Jin6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA, United StatesDepartment of Chemical Engineering, Indian Institute of Technology, Tirupati, Andhra Pradesh, IndiaDepartment of Pathology, University of Texas Medical Branch, Galveston, TX, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA, United StatesDepartment of Biology and Chemistry, Changwon National University, Changwon, Republic of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA, United StatesMacrophages (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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1044834/fullmacrophage activationinflammationbacterial infectionOMVbacteriacaveolin-1 |
| spellingShingle | Ayyanar Sivanantham Ward Alktaish Selvakumar Murugeasan Bin Gong Heedoo Lee Heedoo Lee Yang Jin Caveolin-1 regulates OMV-induced macrophage pro-inflammatory activation and multiple Toll-like receptors Frontiers in Immunology macrophage activation inflammation bacterial infection OMV bacteria caveolin-1 |
| 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 | macrophage activation inflammation bacterial infection OMV bacteria caveolin-1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1044834/full |
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