Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge
The rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as Escherichia coli (E. coli). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and sple...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.597595/full |
| _version_ | 1818418413716897792 |
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| author | Goda Juzenaite Judith Secklehner Judith Secklehner Juho Vuononvirta Juho Vuononvirta Yoseph Helbawi John B. G. Mackey John B. G. Mackey Charlotte Dean James A. Harker James A. Harker Leo M. Carlin Leo M. Carlin Sara Rankin Katia De Filippo |
| author_facet | Goda Juzenaite Judith Secklehner Judith Secklehner Juho Vuononvirta Juho Vuononvirta Yoseph Helbawi John B. G. Mackey John B. G. Mackey Charlotte Dean James A. Harker James A. Harker Leo M. Carlin Leo M. Carlin Sara Rankin Katia De Filippo |
| author_sort | Goda Juzenaite |
| collection | DOAJ |
| description | The rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as Escherichia coli (E. coli). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and spleen intravital microscopy and 3D ex vivo culture of living precision cut splenic slices in combination with fluorescent labelling of endogenous leukocytes. Within seconds after challenge, intravascular marginated neutrophils and lung endothelial cells (ECs) work cooperatively to capture pathogens. Neutrophils retained on lung ECs slow their velocity and aggregate in clusters that enlarge as circulating neutrophils carrying E. coli stop within the microvasculature. The absolute number of splenic neutrophils does not change following challenge; however, neutrophils increase their velocity, migrate to the marginal zone (MZ) and form clusters. Irrespective of their location all neutrophils capturing heat-inactivated E. coli take on an activated phenotype showing increasing surface CD11b. At a molecular level we show that neutralization of ICAM-1 results in splenic neutrophil redistribution to the MZ under homeostasis. Following challenge, splenic levels of CXCL12 and ICAM-1 are reduced allowing neutrophils to migrate to the MZ in a CD29-integrin dependent manner, where the enlargement of splenic neutrophil clusters is CXCR2-CXCL2 dependent. We show directly molecular mechanisms that allow tissue resident neutrophils to provide the first lines of antimicrobial defense by capturing circulating E. coli and forming clusters both in the microvessels of the lung and in the parenchyma of the spleen. |
| first_indexed | 2024-12-14T12:22:17Z |
| format | Article |
| id | doaj.art-67efe035c82742a48b93c25118ed42a5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T12:22:17Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-67efe035c82742a48b93c25118ed42a52022-12-21T23:01:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.597595597595Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli ChallengeGoda Juzenaite0Judith Secklehner1Judith Secklehner2Juho Vuononvirta3Juho Vuononvirta4Yoseph Helbawi5John B. G. Mackey6John B. G. Mackey7Charlotte Dean8James A. Harker9James A. Harker10Leo M. Carlin11Leo M. Carlin12Sara Rankin13Katia De Filippo14National Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomNational Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomCancer Research UK Beatson Institute, Glasgow, United KingdomNational Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomWilliam Harvey Heart Centre, Barts & the London School of Medicine & Dentistry, Queen Mary University of London, London, United KingdomNational Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomNational Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomCancer Research UK Beatson Institute, Glasgow, United KingdomNational Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomNational Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomAsthma UK Centre for Allergic Mechanisms of Asthma, London, United KingdomCancer Research UK Beatson Institute, Glasgow, United KingdomInstitute of Cancer Sciences, University of Glasgow, Glasgow, United KingdomNational Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomNational Heart and Lung Institute (NHLI), Imperial College London, London, United KingdomThe rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as Escherichia coli (E. coli). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and spleen intravital microscopy and 3D ex vivo culture of living precision cut splenic slices in combination with fluorescent labelling of endogenous leukocytes. Within seconds after challenge, intravascular marginated neutrophils and lung endothelial cells (ECs) work cooperatively to capture pathogens. Neutrophils retained on lung ECs slow their velocity and aggregate in clusters that enlarge as circulating neutrophils carrying E. coli stop within the microvasculature. The absolute number of splenic neutrophils does not change following challenge; however, neutrophils increase their velocity, migrate to the marginal zone (MZ) and form clusters. Irrespective of their location all neutrophils capturing heat-inactivated E. coli take on an activated phenotype showing increasing surface CD11b. At a molecular level we show that neutralization of ICAM-1 results in splenic neutrophil redistribution to the MZ under homeostasis. Following challenge, splenic levels of CXCL12 and ICAM-1 are reduced allowing neutrophils to migrate to the MZ in a CD29-integrin dependent manner, where the enlargement of splenic neutrophil clusters is CXCR2-CXCL2 dependent. We show directly molecular mechanisms that allow tissue resident neutrophils to provide the first lines of antimicrobial defense by capturing circulating E. coli and forming clusters both in the microvessels of the lung and in the parenchyma of the spleen.https://www.frontiersin.org/articles/10.3389/fimmu.2021.597595/fullintravital microscopyE. coli challengeneutrophil activationintravascular neutrophilssplenic resident neutrophils |
| spellingShingle | Goda Juzenaite Judith Secklehner Judith Secklehner Juho Vuononvirta Juho Vuononvirta Yoseph Helbawi John B. G. Mackey John B. G. Mackey Charlotte Dean James A. Harker James A. Harker Leo M. Carlin Leo M. Carlin Sara Rankin Katia De Filippo Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge Frontiers in Immunology intravital microscopy E. coli challenge neutrophil activation intravascular neutrophils splenic resident neutrophils |
| title | Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge |
| title_full | Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge |
| title_fullStr | Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge |
| title_full_unstemmed | Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge |
| title_short | Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge |
| title_sort | lung marginated and splenic murine resident neutrophils constitute pioneers in tissue defense during systemic e coli challenge |
| topic | intravital microscopy E. coli challenge neutrophil activation intravascular neutrophils splenic resident neutrophils |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.597595/full |
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