Invariant natural killer T cells act as an extravascular cytotoxic barrier for joint-invading Lyme Borrelia

Maria-Jesus Sanz, Connie H. Y. Wong, Pierre-Olivier Hardy, Aydan Salman-Dilgimen, Tara J. Moriart, George Chaconas, Adriana Marques, Roman Krawetz, Christopher H. Mody, Paul Kubes


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.


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One Comment

  1. Ok, so the joints are more susceptible to infection because natural killer cells made by the liver can’t get to them. What a lot of scientific gobble-d-gook.

    Once Lyme gets into the Cerebrospinal Fluid then it gets to the joints. How about injecting antibiotics directly into said spinal fluid directly? Can abx be injected directly into the spinal fluid safely?

    These “scientists” keep trying to imply that Lyme is a problem because of the body’s own immunological failure of some sort. This is the wrong attitude IMO.

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