Invariant natural killer T cells act as an extravascular cytotoxic barrier for joint-invading Lyme Borrelia
| Autor: | Maria-Jesus Sanz, Pierre-Olivier Hardy, Christopher H. Mody, Tara J. Moriarty, Adriana Marques, Woo-Yong Lee, Roman Krawetz, George Chaconas, Connie H.Y. Wong, Aydan Salman-Dilgimen, Paul Kubes |
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| Rok vydání: | 2014 |
| Předmět: |
Cell
Mice Transgenic Spleen joint iNKT cells Granzymes Mice granzyme B medicine Animals Humans Cytotoxic T cell Borrelia burgdorferi Immunity Cellular Lyme Disease Mice Inbred BALB C Multidisciplinary biology Lyme arthritis Natural killer T cell biology.organism_classification Granzyme B medicine.anatomical_structure Liver Granzyme Organ Specificity CD1D Immunology biology.protein Natural Killer T-Cells Joints Joint Diseases |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Vol. 111 Issue 38: pp. 13936-13941 RODERIC. Repositorio Institucional de la Universitat de Valéncia instname |
| Popis: | CXCR6-GFP(+) cells, which encompass 70% invariant natural killer T cells (iNKT cells), have been found primarily patrolling inside blood vessels in the liver. Although the iNKT cells fail to interact with live pathogens, they do respond to bacterial glycolipids presented by CD1d on liver macrophage that have caught the microbe. In contrast, in this study using dual laser multichannel spinning-disk intravital microscopy of joints, the CXCR6-GFP, which also made up 60-70% iNKT cells, were not found in the vasculature but rather closely apposed to and surrounding the outside of blood vessels, and to a lesser extent throughout the extravascular space. These iNKT cells also differed in behavior, responding rapidly and directly to joint-homing pathogens like Borrelia burgdorferi, which causes Lyme disease. These iNKT cells interacted with B. burgdorferi at the vessel wall and disrupted dissemination attempts by these microbes into joints. Successful penetrance of B. burgdorferi out of the vasculature and into the joint tissue was met by a lethal attack by extravascular iNKT cells through a granzyme-dependent pathway, an observation also made in vitro for iNKT cells from joint but not liver or spleen. These results suggest a novel, critical extravascular iNKT cell immune surveillance in joints that functions as a cytotoxic barrier and explains a large increase in pathogen burden of B. burgdorferi in the joint of iNKT cell-deficient mice, and perhaps the greater susceptibility of humans to this pathogen because of fewer iNKT cells in human joints. |
| Databáze: | OpenAIRE |
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