Étude des interactions entre Streptococcus suis et des neutrophiles porcins

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Acute invariant NKT cell activation triggers an immune response that drives prominent changes in iron homeostasis

Iron homeostasis is an essential biological process that ensures the tissue distribution of iron for various cellular processes. As the major producer of hepcidin, the liver is central to the regulation of iron metabolism. The liver is also home to many immune cells, which upon activation may greatly impact iron metabolism. Here, we focus on the role of invariant natural killer T (iNKT) cells, a subset of T lymphocytes that, in mice, is most abundant in the liver. Activation of iNKT cells with the prototypical glycosphingolipid antigen, α-galactosylceramide, resulted in immune cell proliferation and biphasic changes in iron metabolism. This involved an early phase characterized by hypoferremia, hepcidin induction and ferroportin suppression, and a second phase associated with strong suppression of hepcidin despite elevated levels of circulating and tissue iron. We further show that these changes in iron metabolism are fully dependent on iNKT cell activation. Finally, we demonstrate that the biphasic regulation of hepcidin is independent of NK and Kupfer cells, and is initially driven by the STAT3 infammatory pathway, whereas the second phase is regulated by repression of the BMP/SMAD signaling pathway. These fndings indicate that iNKT activation and the resulting cell proliferation infuence iron homeostasis

Acute invariant NKT cell activation triggers an immune response that drives prominent changes in iron homeostasis

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licen ses/by/4.0/.Iron homeostasis is an essential biological process that ensures the tissue distribution of iron for various cellular processes. As the major producer of hepcidin, the liver is central to the regulation of iron metabolism. The liver is also home to many immune cells, which upon activation may greatly impact iron metabolism. Here, we focus on the role of invariant natural killer T (iNKT) cells, a subset of T lymphocytes that, in mice, is most abundant in the liver. Activation of iNKT cells with the prototypical glycosphingolipid antigen, α-galactosylceramide, resulted in immune cell proliferation and biphasic changes in iron metabolism. This involved an early phase characterized by hypoferremia, hepcidin induction and ferroportin suppression, and a second phase associated with strong suppression of hepcidin despite elevated levels of circulating and tissue iron. We further show that these changes in iron metabolism are fully dependent on iNKT cell activation. Finally, we demonstrate that the biphasic regulation of hepcidin is independent of NK and Kupffer cells, and is initially driven by the STAT3 inflammatory pathway, whereas the second phase is regulated by repression of the BMP/SMAD signaling pathway. These findings indicate that iNKT activation and the resulting cell proliferation influence iron homeostasis.This work was supported by grants from the Canadian Institutes of Health Research (CIHR, Grant no. PJT-159775) and Natural Sciences and Engineering Research Council of Canada (NSERC, Grant RGPIN-2018-06442) to MMS. HH received a PhD scholarship from the NSERC. SL is a Research Scholars Emeritus awardee from the FRQS.info:eu-repo/semantics/publishedVersio

High-throughput refractive index-based microphotonic sensor for enhanced cellular discrimination

This paper presents a novel microphotonic sensor based on silicon technologies for high-throughput single cell measurements. It employs a highly sensitive Fabry-Pérot resonant cavity to extract cellular refractive index information. The integrated large cross-section rib waveguides provide a single-mode like behavior important for resonant cell sensing. Differentiated myeloid cells derived from a promyelocytic leukemia cell line were injected in a microchannel, sheathlessly focused using inertial forces and analyzed while flowing through the resonant cavity volume. Results were compared against a commercial flow cytometer and showed a substantial improvement on cellular discrimination. Thus, this sensor has the ability to discriminate cell populations, usually identified using fluorescent parameters, without any dyes and can reach measurement rate as high as 2000 cells per second. By harnessing the cell's effective volume refractive index, our device offers complementary measurements readily improving actual technologies and thus providing crucial information for research and clinical professionals

Immature and mature bone marrow-derived dendritic cells exhibit distinct intracellular mechanical properties

ABSTRACT: Dendritic cells (DCs) patrol the organism at an immature stage to detect the presence of pathogens. Once activated, these mature DCs reach the lymph nodes to activate antigen-specific T lymphocytes and thus initiate an adaptative immune response to control the pathogen. The migration of both immature and mature DCs is a key process for their optimal function. DC migration requires transit through narrow constrictions that is allowed by their high local and global deformation capabilities. In addition to cytoplasmic changes, the nucleus mechanical properties also have a major impact for cellular migration and motility. Yet, nucleus intracellular mobility of dendritic cells or its variation upon maturation have not been investigated. Our study defines the biophysical phenotypic variations of dendritic cells upon maturation using interferometric deformability cytometry. This method characterizes different cellular mechanical properties, such as elongation and nucleus offset, by assessing the refractive index spatial distribution of shear-induced deformed cells. By using these parameters, our data suggest that in vitro bone marrow derived dendritic cell (BMDC) maturation induces cell stiffening and reduces nucleus mobility, allowing to distinguish immature and mature dendritic cells. Overall, our method provides insights on intracellular mechanical properties of two dendritic cell states

Nearby Construction Impedes the Progression to Overt Autoimmune Diabetes in NOD Mice

Construction nearby animal houses has sporadically been reported to affect various aspects of animal health. Most of the reports have focussed on the impact on stress hormone levels and the hypersensitivity of animals relative to humans. There has also been an anecdotal report on the impact of construction on autoimmune diabetes in NOD mice. Here, we describe that nearby construction significantly impedes the progression to overt diabetes in female NOD mice offspring. We demonstrate that this was not due to a genetic drift or to particularities associated with our specific mouse colony. Interestingly, although the glycemia levels remained low in mice born from mothers subject to construction stress during gestation, we detected an active autoimmune reaction towards pancreatic islet cells, as measured by both the degree of insulitis and the presence of insulin autoantibody levels in the serum. These results suggest that the external stress imposed during embryonic development does not prevent but significantly delays the autoimmune process. Together, our findings emphasize the impact of surrounding factors during in vivo studies and are in agreement with the hypothesis that both environmental and genetic cues contribute to autoimmune diabetes development