Vimentin regulates mitochondrial ROS production and inflammatory responses of neutrophils.

Autor:	Huynh TN; Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States., Toperzer J; Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States., Scherer A; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States.; Department of Medicine, Harvard Medical School, Boston, MA, United States., Gumina A; Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States., Brunetti T; Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States., Mansour MK; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States.; Department of Medicine, Harvard Medical School, Boston, MA, United States., Markovitz DM; Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, United States., Russo BC; Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jul 30; Vol. 15, pp. 1416275. Date of Electronic Publication: 2024 Jul 30 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1416275
Abstrakt:	The intermediate filament vimentin is present in immune cells and is implicated in proinflammatory immune responses. Whether and how it supports antimicrobial activities of neutrophils are not well established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin. We demonstrate that vimentin restricts the production of proinflammatory cytokines and reactive oxygen species (ROS), but enhances phagocytosis and swarming. We observe that vimentin is dispensable for neutrophil extracellular trap (NET) formation, degranulation, and inflammasome activation. Moreover, gene expression analysis demonstrated that the presence of vimentin was associated with changes in expression of multiple genes required for mitochondrial function and ROS overproduction. Treatment of wild-type cells with rotenone, an inhibitor for complex I of the electron transport chain, increases the ROS levels. Likewise, treatment with mitoTEMPO, a SOD mimetic, rescues the ROS production in cells lacking vimentin. Together, these data show vimentin regulates neutrophil antimicrobial functions and alters ROS levels through regulation of mitochondrial activity. Competing Interests: MM consults for NED Biosystems, Vericel. He received grants from Karius, Danaher, Genentech, and Thermo-Fisher Scientific. He is a medical writer for UpToDate. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Huynh, Toperzer, Scherer, Gumina, Brunetti, Mansour, Markovitz and Russo.)
Databáze:	MEDLINE
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