Title |
Invariant natural killer T cells act as an extravascular cytotoxic barrier for joint-invading Lyme Borrelia
|
---|---|
Published in |
Proceedings of the National Academy of Sciences of the United States of America, September 2014
|
DOI | 10.1073/pnas.1404769111 |
Pubmed ID | |
Authors |
Woo-Yong Lee, Maria-Jesus Sanz, Connie H. Y. Wong, Pierre-Olivier Hardy, Aydan Salman-Dilgimen, Tara J. Moriarty, George Chaconas, Adriana Marques, Roman Krawetz, Christopher H. Mody, Paul Kubes |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Canada | 5 | 20% |
United States | 2 | 8% |
France | 2 | 8% |
Nepal | 1 | 4% |
South Africa | 1 | 4% |
Curaçao | 1 | 4% |
Unknown | 13 | 52% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 15 | 60% |
Scientists | 5 | 20% |
Practitioners (doctors, other healthcare professionals) | 4 | 16% |
Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Switzerland | 1 | 1% |
Netherlands | 1 | 1% |
United Kingdom | 1 | 1% |
Canada | 1 | 1% |
United States | 1 | 1% |
Unknown | 78 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 23 | 28% |
Student > Ph. D. Student | 21 | 25% |
Professor | 6 | 7% |
Student > Doctoral Student | 5 | 6% |
Other | 5 | 6% |
Other | 10 | 12% |
Unknown | 13 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 22 | 27% |
Agricultural and Biological Sciences | 21 | 25% |
Medicine and Dentistry | 11 | 13% |
Biochemistry, Genetics and Molecular Biology | 5 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
Other | 5 | 6% |
Unknown | 16 | 19% |