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

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.

NK1.1+ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8+ T cells in mice

“…IL-7 and IL-15) [30] or access to microenvironmental niches. In this context, it is noteworthy that CD8 + T RM cells and tissue-resident macrophages have recently been shown to co-operate for homeostatic organ surveillance in SG [31]. The negative regulation of CD8 + T RM cells by NK1.1 + ILC in SG, reported here for the first time, also serves a homeostatic purpose.…”

Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices

“…However, as in the current experimental settings, the collagen matrix falls apart in within 8-12 hours depending on the density. Nevertheless, our conclusion is supported by a recent study, which shows that in vivo in salivary gland, T cells follow trajectories established by macrophages, allowing T cells to migrate faster [43].…”

Locally confined IFNγproduction by CD4+T cells provides niches for murine cytomegalovirus replication in the salivary gland

“…Parameters to describe CD4 + T cell motility within the SMG were determined using data from twophoton intravital microscopy analyses on the dynamics of CD8+ T cells in the SMG during lymphocytic choriomeningitis virus infection (Stolp et al, 2020) assuming similar motility characteristics of both cell types. T cells were observed to move in the SMG with an average speed of 6.8 m/min, a top speed of 18 m/min and were characterized with a low arrest coefficient (Stolp et al, 2020). Thus, these data indicate a fast motion with rare motility arrest and frequent direction changes.…”