LPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosis

Abstract Tuberculosis (TB) is now the leading cause of death globally from a single infectious disease. So far, the exact mechanism of anti-tuberculosis immunity has not been fully elucidated, and the immune role of neutrophils in anti-tuberculosis infection is controversial. We investigated the kil...

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Main Authors: Lina Jiang, Zhenxing Su, Yangxiao Zhang, Hongsheng Liu, Hongtao Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-12232-y
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author Lina Jiang
Zhenxing Su
Yangxiao Zhang
Hongsheng Liu
Hongtao Wang
author_facet Lina Jiang
Zhenxing Su
Yangxiao Zhang
Hongsheng Liu
Hongtao Wang
author_sort Lina Jiang
collection DOAJ
description Abstract Tuberculosis (TB) is now the leading cause of death globally from a single infectious disease. So far, the exact mechanism of anti-tuberculosis immunity has not been fully elucidated, and the immune role of neutrophils in anti-tuberculosis infection is controversial. We investigated the killing function of neutrophils against Mycobacterium tuberculosis (M.tb) and the effect of neutrophils activated by lipopolysaccharide (LPS) on the production of reactive oxygen species (ROS), to evaluate the mechanism by which neutrophils eradicate M.tb mediated infection and find theoretical basis for clinical treatment of tuberculosis. The killing rate of neutrophils to FDA (Fluorescein diacetate)-labeled M.tb was detected by flow cytometry, and the killing rate of neutrophils to M.tb was observed by fluorescence microscopy. The activation rate and ROS production of neutrophils were observed at different time points after M.tb infection. Flow cytometry was utilized to detect the effect of LPS on the ROS production during neutrophil mediated killing of M.tb. Toll-like receptor 4 (TLR4) monoclonal antibody or NADPH oxidase inhibitor was utilized to detect the LPS activated neutrophil mediated production of ROS during M.tb killing. The killing function of neutrophils against M.tb increased with time. The activation rate and ROS production of neutrophils increased with time after M.tb infection. The activation rate and ROS production of neutrophils increased with the increase of LPS concentration. The activation rate and ROS production of PMN were reduced by TLR4 monoclonal antibody or NADPH oxidase inhibitor.LPS-TLR4 pathway is involved in neutrophils induced ROS mediated killing of M.tb. LPS promotes neutrophils mediated killing of M.tb, through ROS mediated production of NADPH oxidase which provides a theoretical basis for testing the role of neutrophils in clearance of M.tb in humans, and reducing the M.tb pathogenesis.
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spelling doaj-art-604e9ba2fe934b9f992df90c197f55482025-08-20T03:42:45ZengNature PortfolioScientific Reports2045-23222025-07-011511810.1038/s41598-025-12232-yLPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosisLina Jiang0Zhenxing Su1Yangxiao Zhang2Hongsheng Liu3Hongtao Wang4School of Stomatology, Bengbu Medical UniversitySchool of Basic Medicine, Bengbu Medical UniversitySchool of Basic Medicine, Bengbu Medical UniversitySchool of Stomatology, Bengbu Medical UniversitySchool of Laboratory Medicine, Bengbu Medical UniversityAbstract Tuberculosis (TB) is now the leading cause of death globally from a single infectious disease. So far, the exact mechanism of anti-tuberculosis immunity has not been fully elucidated, and the immune role of neutrophils in anti-tuberculosis infection is controversial. We investigated the killing function of neutrophils against Mycobacterium tuberculosis (M.tb) and the effect of neutrophils activated by lipopolysaccharide (LPS) on the production of reactive oxygen species (ROS), to evaluate the mechanism by which neutrophils eradicate M.tb mediated infection and find theoretical basis for clinical treatment of tuberculosis. The killing rate of neutrophils to FDA (Fluorescein diacetate)-labeled M.tb was detected by flow cytometry, and the killing rate of neutrophils to M.tb was observed by fluorescence microscopy. The activation rate and ROS production of neutrophils were observed at different time points after M.tb infection. Flow cytometry was utilized to detect the effect of LPS on the ROS production during neutrophil mediated killing of M.tb. Toll-like receptor 4 (TLR4) monoclonal antibody or NADPH oxidase inhibitor was utilized to detect the LPS activated neutrophil mediated production of ROS during M.tb killing. The killing function of neutrophils against M.tb increased with time. The activation rate and ROS production of neutrophils increased with time after M.tb infection. The activation rate and ROS production of neutrophils increased with the increase of LPS concentration. The activation rate and ROS production of PMN were reduced by TLR4 monoclonal antibody or NADPH oxidase inhibitor.LPS-TLR4 pathway is involved in neutrophils induced ROS mediated killing of M.tb. LPS promotes neutrophils mediated killing of M.tb, through ROS mediated production of NADPH oxidase which provides a theoretical basis for testing the role of neutrophils in clearance of M.tb in humans, and reducing the M.tb pathogenesis.https://doi.org/10.1038/s41598-025-12232-yLipopolysaccharide (LPS)Reactive oxygen species (ROS)NeutrophilsTuberculosis
spellingShingle Lina Jiang
Zhenxing Su
Yangxiao Zhang
Hongsheng Liu
Hongtao Wang
LPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosis
Scientific Reports
Lipopolysaccharide (LPS)
Reactive oxygen species (ROS)
Neutrophils
Tuberculosis
title LPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosis
title_full LPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosis
title_fullStr LPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosis
title_full_unstemmed LPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosis
title_short LPS promotes the production of ROS in neutrophils to regulate their killing activity against Mycobacterium tuberculosis
title_sort lps promotes the production of ros in neutrophils to regulate their killing activity against mycobacterium tuberculosis
topic Lipopolysaccharide (LPS)
Reactive oxygen species (ROS)
Neutrophils
Tuberculosis
url https://doi.org/10.1038/s41598-025-12232-y
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