Salivary gland macrophages and tissue-resident CD8+ T cells cooperate for homeostatic organ surveillance
Salivary gland macrophages and tissue-resident CD8+ T cells cooperate for homeostatic organ surveillance
It is well established that tissue macrophages and tissue-resident memory CD8+ T cells (TRM) play important roles for pathogen sensing and rapid protection of barrier tissues. In contrast, the mechanisms by which these two cell types cooperate for homeostatic organ surveillance after clearance of infections is poorly understood. Here, we used intravital imaging to show that TRM dynamically followed tissue macrophage topology in noninflamed murine submandibular salivary glands (SMGs). Depletion of tissue macrophages interfered with SMG TRM motility and caused a reduction of interepithelial T cell crossing. In the absence of macrophages, SMG TRM failed to cluster in response to local inflammatory chemokines. A detailed analysis of the SMG microarchitecture uncovered discontinuous attachment of tissue macrophages to neighboring epithelial cells, with occasional macrophage protrusions bridging adjacent acini and ducts. When dissecting the molecular mechanisms that drive homeostatic SMG TRM motility, we found that these cells exhibit a wide range of migration modes: In addition to chemokine- and adhesion receptor-driven motility, resting SMG TRM displayed a remarkable capacity for autonomous motility in the absence of chemoattractants and adhesive ligands. Autonomous SMG TRM motility was mediated by friction and insertion of protrusions into gaps offered by the surrounding microenvironment. In sum, SMG TRM display a unique continuum of migration modes, which are supported in vivo by tissue macrophages to allow homeostatic patrolling of the complex SMG architecture.
Animals, CD8-Positive T-Lymphocytes/immunology, Homeostasis/immunology, Macrophages/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Organ Specificity/immunology, Salivary Glands/immunology, Surveys and Questionnaires
Stolp, Bettina
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Thelen, Flavian
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Ficht, Xenia
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Altenburger, Lukas M.
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Ruef, Nora
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Krishna Inavalli, V. V.G.
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Germann, Philipp
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Page, Nicolas
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Moalli, Federica
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Raimondi, Andrea
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Keyser, Kirsten A.
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Morteza Seyed Jafari, S.
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Barone, Francesca
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Dettmer, Matthias S.
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Merkler, Doron
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Iannacone, Matteo
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Sharpe, James
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Schlapbach, Christoph
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Fackler, Oliver T.
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Valentin Nägerl, U.
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Stein, Jens V.
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3 April 2020
Stolp, Bettina
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Thelen, Flavian
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Ficht, Xenia
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Altenburger, Lukas M.
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Ruef, Nora
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Krishna Inavalli, V. V.G.
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Germann, Philipp
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Page, Nicolas
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Moalli, Federica
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Raimondi, Andrea
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Keyser, Kirsten A.
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Morteza Seyed Jafari, S.
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Barone, Francesca
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Dettmer, Matthias S.
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Merkler, Doron
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Iannacone, Matteo
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Sharpe, James
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Schlapbach, Christoph
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Fackler, Oliver T.
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Valentin Nägerl, U.
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Stein, Jens V.
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Stolp, Bettina, Thelen, Flavian, Ficht, Xenia, Altenburger, Lukas M., Ruef, Nora, Krishna Inavalli, V. V.G., Germann, Philipp, Page, Nicolas, Moalli, Federica, Raimondi, Andrea, Keyser, Kirsten A., Morteza Seyed Jafari, S., Barone, Francesca, Dettmer, Matthias S., Merkler, Doron, Iannacone, Matteo, Sharpe, James, Schlapbach, Christoph, Fackler, Oliver T., Valentin Nägerl, U. and Stein, Jens V.
(2020)
Salivary gland macrophages and tissue-resident CD8+ T cells cooperate for homeostatic organ surveillance.
Science immunology, 5 (46), [eaaz4371].
(doi:10.1126/sciimmunol.aaz4371).
Abstract
It is well established that tissue macrophages and tissue-resident memory CD8+ T cells (TRM) play important roles for pathogen sensing and rapid protection of barrier tissues. In contrast, the mechanisms by which these two cell types cooperate for homeostatic organ surveillance after clearance of infections is poorly understood. Here, we used intravital imaging to show that TRM dynamically followed tissue macrophage topology in noninflamed murine submandibular salivary glands (SMGs). Depletion of tissue macrophages interfered with SMG TRM motility and caused a reduction of interepithelial T cell crossing. In the absence of macrophages, SMG TRM failed to cluster in response to local inflammatory chemokines. A detailed analysis of the SMG microarchitecture uncovered discontinuous attachment of tissue macrophages to neighboring epithelial cells, with occasional macrophage protrusions bridging adjacent acini and ducts. When dissecting the molecular mechanisms that drive homeostatic SMG TRM motility, we found that these cells exhibit a wide range of migration modes: In addition to chemokine- and adhesion receptor-driven motility, resting SMG TRM displayed a remarkable capacity for autonomous motility in the absence of chemoattractants and adhesive ligands. Autonomous SMG TRM motility was mediated by friction and insertion of protrusions into gaps offered by the surrounding microenvironment. In sum, SMG TRM display a unique continuum of migration modes, which are supported in vivo by tissue macrophages to allow homeostatic patrolling of the complex SMG architecture.
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More information
Accepted/In Press date: 10 March 2020
Published date: 3 April 2020
Additional Information:
Funding Information:
This work was funded by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457, and 31003A_172994 (to J.V.S.); Leopoldina fellowship LPDS 2011-16 (to B.S.); the Deutsche Forschungsgemeinschaft (German research foundation, DFG)-project number 240245660-SFB1129 (project 8) (to B.S. and O.T.F.) and SFB900 (to K.A.K.); and the Novartis foundation fellowship 16C193 (to F.T.). P.G. and J.S. acknowledge support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013-2017,” and support of the CERCA Programme/Generalitat de Catalunya.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
Keywords:
Animals, CD8-Positive T-Lymphocytes/immunology, Homeostasis/immunology, Macrophages/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Organ Specificity/immunology, Salivary Glands/immunology, Surveys and Questionnaires
Identifiers
Local EPrints ID: 467868
URI: http://eprints.soton.ac.uk/id/eprint/467868
ISSN: 2470-9468
PURE UUID: bd46b175-9e66-4ae6-a219-22db9fe400cf
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Date deposited: 22 Jul 2022 16:41
Last modified: 17 Mar 2024 04:04
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Contributors
Author:
Bettina Stolp
Author:
Flavian Thelen
Author:
Xenia Ficht
Author:
Lukas M. Altenburger
Author:
Nora Ruef
Author:
V. V.G. Krishna Inavalli
Author:
Philipp Germann
Author:
Nicolas Page
Author:
Federica Moalli
Author:
Andrea Raimondi
Author:
Kirsten A. Keyser
Author:
S. Morteza Seyed Jafari
Author:
Francesca Barone
Author:
Matthias S. Dettmer
Author:
Doron Merkler
Author:
Matteo Iannacone
Author:
James Sharpe
Author:
Christoph Schlapbach
Author:
Oliver T. Fackler
Author:
U. Valentin Nägerl
Author:
Jens V. Stein
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