Research ArticleCELL MIGRATION

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

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Science Immunology  03 Apr 2020:
Vol. 5, Issue 46, eaaz4371
DOI: 10.1126/sciimmunol.aaz4371

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Salivary Gland Surveillance

Pathogen sensing in tissues is critical to generating rapid immune responses. Within these tissues, macrophages and resident memory CD8+ T cells (TRM) work together to detect pathogens, and Stolp et al. use intravital imaging of submandibular salivary glands (SMG) to show that TRM follow tissue macrophage topology in a dynamic manner. Macrophage depletion is associated with reduced TRM motility and a diminished clustering in response to inflammatory chemokines. However, although SMG TRM respond to chemoattractants, autonomous motility is also observed and is mediated by friction and insertion of cellular protrusions into microenvironmental gaps. These findings demonstrate that SMG TRM can use different motility modes in proximity to tissue macrophages to patrol the tissue microenvironment.


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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