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

Frontiers in Immunology

Immunology

Selvakumar Murugeasan¹  Bin Gong²  Yang Jin³  Ayyanar Sivanantham³  Ward Alktaish³  Heedoo Lee⁴ 

[1] Department of Chemical Engineering, Indian Institute of Technology, Tirupati, Andhra Pradesh, India;Department of Pathology, University of Texas Medical Branch, Galveston, TX, United States;Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA, United States;Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University, Boston, MA, United States;Department of Biology and Chemistry, Changwon National University, Changwon, Republic of Korea;

关键词: macrophage activation;    inflammation;    bacterial infection;    OMV;    bacteria;    caveolin-1;    TLRs;   

DOI  :  10.3389/fimmu.2023.1044834

 received in 2022-09-15, accepted in 2023-01-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Sivanantham, Alktaish, Murugeasan, Gong, Lee and Jin