Biology subjects

Page, N.

Publications and source records attributed to Page, N..

22 records · Page 2Linked to original sources

bioRxiv2020

Cold Exposure Protects from Neuroinflammation Through Immunologic Reprogramming

Autoimmunity is energetically costly, but the impact of a metabolically active state on immunity and immune-mediated diseases is unclear. Ly6Chi monocytes are key effectors in CNS autoimmunity with elusive role in priming naive autoreactive T cells. Here we provide unbiased analysis of the immune changes in various compartments during cold exposure, and show that this energetically costly stimulus markedly ameliorates active experimental autoimmune encephalomyelitis (EAE). Cold exposure decreases MHCII on monocytes at steady-state and in various inflammatory mouse models, and suppresses T cell priming and pathogenicity through the modulation of monocytes. Genetic, or antibody-mediated monocyte depletion, or adoptive transfer of Th1- or Th17-polarized cells for EAE abolish the cold-induced effects on T cells or EAE, respectively. These findings provide a mechanistic link between environmental temperature and neuroinflammation, and suggest competition between cold-induced metabolic adaptations and autoimmunity as energetic trade-off beneficial for the immune-mediated diseases.

immunology↗

bioRxiv2020

The critical ecological role of an endemic, large-bodied frugivore on a small tropical island

Endozoochory, a mutualistic interaction between plants and frugivores, is one of the key processes responsible for maintenance of tropical biodiversity. Islands, which have a smaller subset of plants and frugivores when compared with mainland communities, offer an interesting setting to understand the organization of plant-frugivore communities vis-a-vis the mainland sites. We examined the relative influence of functional traits and phylogenetic relationships on the plant-seed disperser interactions on an island and a mainland site. The island site allowed us to investigate the organization of the plant-seed disperser community in the natural absence of key frugivore groups (bulbuls and barbets) of Asian tropics. The endemic Narcondam Hornbill, was the most abundant frugivore on the island and played a central role in the community. Species strength, a measure of relevance of frugivores for plants, of frugivores was positively associated with their abundance. Among plants, figs had the highest species strength and played a central role in the community. Island-mainland comparison revealed that the island plant-seed disperser community was more asymmetric, connected and nested as compared to the mainland community. Neither phylogenetic relationships or functional traits (after controlling for phylogenetic relationships) were able to explain the patterns of interactions between plants and frugivores on the island or the mainland pointing towards the diffused nature of plant-frugivore interactions. The diffused nature is a likely consequence of plasticity in foraging behavior and trait convergence that contribute to governing the interactions between plants and frugivores.

ecology↗

bioRxiv2019

Salivary gland macrophages assist tissue-resident CD8+ T cell immune surveillance

Tissue macrophages and tissue resident memory CD8+ T cells (TRM) play important roles for pathogen sensing and rapid protection of barrier tissues. To date, it is incompletely understood how these two cell types cooperate for efficient organ surveillance during homeostasis. Here, we used intravital imaging to show that TRM dynamically crawled along tissue macrophages in murine submandibular salivary glands (SMG) during the memory phase following a viral infection. Ex vivo confined SMG TRM integrated an unexpectedly wide range of migration modes: in addition to chemokine-and adhesion receptor-driven motility, SMG TRM displayed a remarkable capacity of autonomous motility in the absence of chemoattractants and adhesive ligands. This unique intrinsic SMG TRM motility was transmitted by friction and adaptation to microenvironmental topography through protrusion insertion into permissive gaps. Analysis of extracellular space in SMG using super-resolution shadow imaging showed discontinuous attachment of tissue macrophages to neighboring epithelial cells, offering paths of least resistance for patrolling TRM. Upon tissue macrophage depletion, intraepithelial SMG TRM showed decreased motility and reduced epithelial crossing events, and failed to cluster in response to local inflammatory chemokine stimuli. In sum, our data uncover a continuum of SMG TRM migration modes and identify a new accessory function of tissue macrophages to facilitate TRM patrolling of the complex exocrine gland architecture.\n\nOne sentence summaryCombined in vitro and in vivo imaging of salivary gland-resident tissue memory CD8+ T cells (TRM) uncovers their unique migratory behavior and describes a novel accessory function of tissue macrophages to assist TRM surveillance.

immunology↗

bioRxiv2018

In vivo function of the lipid raft protein Flotillin 1 during CD8+ T cell-mediated host surveillance

Flotillin-1 (Flot1) is a highly conserved, ubiquitously expressed lipid raft-associated scaffolding protein. Migration of Flot1-deficient neutrophils is impaired due to a decrease in myosin II-mediated contractility. Flot1 also accumulates in the uropod of polarized T cells, suggesting an analogous role in T cell migration. Here, we analyzed morphology and migration of naive and memory WT and Flot1-/- CD8+ T cells in lymphoid and non-lymphoid tissues with intravital two-photon microscopy, as well as their clonal expansion during antiviral immune responses. Flot1-/- CD8+ T cells displayed minor alterations in cell shape and motility parameters in vivo but showed comparable homing to lymphoid organs and infiltration into non-lymphoid tissues. Taken together, Flot1 plays a detectable but unexpectedly minor role for CD8+ T cell behavior under physiological conditions.

immunology↗