Journal article

Salivary gland macrophages and tissue-resident CD8+ T cells cooperate for homeostatic organ surveillance.

  • Stolp B Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
  • Thelen F Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
  • Ficht X Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
  • Altenburger LM Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland.
  • Ruef N Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland.
  • Inavalli VVGK University of Bordeaux, 33700 Bordeaux, France.
  • Germann P EMBL Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain.
  • Page N Department of Pathology and Immunology, Division of Clinical Pathology, University and University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Moalli F IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
  • Raimondi A IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
  • Keyser KA Institute for Virology, OE5230, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
  • Seyed Jafari SM Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Barone F Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
  • Dettmer MS Institute of Pathology, University of Bern, 3008 Bern, Switzerland.
  • Merkler D Department of Pathology and Immunology, Division of Clinical Pathology, University and University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Iannacone M IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
  • Sharpe J EMBL Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain.
  • Schlapbach C Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Fackler OT Department for Infectious Diseases, Integrative Virology, Center for Integrative Infectious Disease Research, University Hospital Heidelberg, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany.
  • Nägerl UV University of Bordeaux, 33700 Bordeaux, France.
  • Stein JV Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700 Fribourg, Switzerland. jens.stein@unifr.ch.
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  • 2020-04-05
Published in:
  • Science immunology. - 2020
English 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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  • English
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https://sonar.ch/global/documents/239470
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