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 (T ) 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 infe...
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| Veröffentlicht in: | Science immunology Jg. 5; H. 46 |
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| Abstract | It is well established that tissue macrophages and tissue-resident memory CD8
T cells (T
) 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 T
dynamically followed tissue macrophage topology in noninflamed murine submandibular salivary glands (SMGs). Depletion of tissue macrophages interfered with SMG T
motility and caused a reduction of interepithelial T cell crossing. In the absence of macrophages, SMG T
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 T
motility, we found that these cells exhibit a wide range of migration modes: In addition to chemokine- and adhesion receptor-driven motility, resting SMG T
displayed a remarkable capacity for autonomous motility in the absence of chemoattractants and adhesive ligands. Autonomous SMG T
motility was mediated by friction and insertion of protrusions into gaps offered by the surrounding microenvironment. In sum, SMG T
display a unique continuum of migration modes, which are supported in vivo by tissue macrophages to allow homeostatic patrolling of the complex SMG architecture. |
|---|---|
| AbstractList | It is well established that tissue macrophages and tissue-resident memory CD8
T cells (T
) 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 T
dynamically followed tissue macrophage topology in noninflamed murine submandibular salivary glands (SMGs). Depletion of tissue macrophages interfered with SMG T
motility and caused a reduction of interepithelial T cell crossing. In the absence of macrophages, SMG T
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 T
motility, we found that these cells exhibit a wide range of migration modes: In addition to chemokine- and adhesion receptor-driven motility, resting SMG T
displayed a remarkable capacity for autonomous motility in the absence of chemoattractants and adhesive ligands. Autonomous SMG T
motility was mediated by friction and insertion of protrusions into gaps offered by the surrounding microenvironment. In sum, SMG T
display a unique continuum of migration modes, which are supported in vivo by tissue macrophages to allow homeostatic patrolling of the complex SMG architecture. 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.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. |
| Author | Inavalli, V V G Krishna Sharpe, James Moalli, Federica Keyser, Kirsten A Ficht, Xenia Raimondi, Andrea Seyed Jafari, S Morteza Barone, Francesca Merkler, Doron Germann, Philipp Stolp, Bettina Stein, Jens V Ruef, Nora Dettmer, Matthias S Schlapbach, Christoph Fackler, Oliver T Page, Nicolas Thelen, Flavian Iannacone, Matteo Altenburger, Lukas M Nägerl, U Valentin |
| Author_xml | – sequence: 1 givenname: Bettina orcidid: 0000-0003-2945-8536 surname: Stolp fullname: Stolp, Bettina organization: Department for Infectious Diseases, Integrative Virology, Center for Integrative Infectious Disease Research, University Hospital Heidelberg, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany – sequence: 2 givenname: Flavian orcidid: 0000-0002-9372-1995 surname: Thelen fullname: Thelen, Flavian organization: Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland – sequence: 3 givenname: Xenia orcidid: 0000-0002-4534-8225 surname: Ficht fullname: Ficht, Xenia organization: Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland – sequence: 4 givenname: Lukas M orcidid: 0000-0002-7998-5484 surname: Altenburger fullname: Altenburger, Lukas M organization: Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland – sequence: 5 givenname: Nora orcidid: 0000-0001-5211-3363 surname: Ruef fullname: Ruef, Nora organization: Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland – sequence: 6 givenname: V V G Krishna orcidid: 0000-0002-7100-0214 surname: Inavalli fullname: Inavalli, V V G Krishna organization: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, 33077 Bordeaux, France – sequence: 7 givenname: Philipp orcidid: 0000-0002-2057-4883 surname: Germann fullname: Germann, Philipp organization: Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain – sequence: 8 givenname: Nicolas surname: Page fullname: Page, Nicolas organization: Department of Pathology and Immunology, Division of Clinical Pathology, University and University Hospitals of Geneva, 1211 Geneva, Switzerland – sequence: 9 givenname: Federica surname: Moalli fullname: Moalli, Federica organization: IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy – sequence: 10 givenname: Andrea orcidid: 0000-0002-4563-386X surname: Raimondi fullname: Raimondi, Andrea organization: IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy – sequence: 11 givenname: Kirsten A surname: Keyser fullname: Keyser, Kirsten A organization: Institute for Virology, OE5230, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany – sequence: 12 givenname: S Morteza orcidid: 0000-0002-6466-2199 surname: Seyed Jafari fullname: Seyed Jafari, S Morteza organization: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland – sequence: 13 givenname: Francesca surname: Barone fullname: Barone, Francesca organization: Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK – sequence: 14 givenname: Matthias S orcidid: 0000-0003-0948-1392 surname: Dettmer fullname: Dettmer, Matthias S organization: Institute of Pathology, University of Bern, 3008 Bern, Switzerland – sequence: 15 givenname: Doron orcidid: 0000-0002-0247-2007 surname: Merkler fullname: Merkler, Doron organization: Department of Pathology and Immunology, Division of Clinical Pathology, University and University Hospitals of Geneva, 1211 Geneva, Switzerland – sequence: 16 givenname: Matteo orcidid: 0000-0002-9370-2671 surname: Iannacone fullname: Iannacone, Matteo organization: IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy – sequence: 17 givenname: James surname: Sharpe fullname: Sharpe, James organization: Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluis Companys 23, 08010 Barcelona, Spain – sequence: 18 givenname: Christoph orcidid: 0000-0003-0258-1243 surname: Schlapbach fullname: Schlapbach, Christoph organization: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland – sequence: 19 givenname: Oliver T surname: Fackler fullname: Fackler, Oliver T organization: Department for Infectious Diseases, Integrative Virology, Center for Integrative Infectious Disease Research, University Hospital Heidelberg, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany – sequence: 20 givenname: U Valentin orcidid: 0000-0001-6831-9008 surname: Nägerl fullname: Nägerl, U Valentin organization: Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, 33077 Bordeaux, France – sequence: 21 givenname: Jens V orcidid: 0000-0002-8199-9586 surname: Stein fullname: Stein, Jens V email: jens.stein@unifr.ch organization: Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland. jens.stein@unifr.ch |
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| Snippet | It is well established that tissue macrophages and tissue-resident memory CD8
T cells (T
) play important roles for pathogen sensing and rapid protection of... 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... |
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| Title | Salivary gland macrophages and tissue-resident CD8 + T cells cooperate for homeostatic organ surveillance |
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