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

Lee, Woo Yong; Sanz, María-Jesús; Wong, Connie Hoi Yee; Hardy, Pierre-Olivier; Salman-Dilgimen, Aydan; Moriarty, Tara J.; Chaconas, George; Marques, Adriana; Krawetz, Roman; Mody, Christopher H.; Kubes, Paul

doi:10.1073/pnas.1404769111

Cited by 57 publications

(81 citation statements)

References 34 publications

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“…NKT cells specifically recognize diacylglycerol antigens from B. burgdorferi (40). They limit spirochete dissemination by killing blood-borne spirochetes in the liver (41) and act as a cytotoxic barrier to prevent spirochete entry into the joint space (42). Deletion of NKT cells resulted in more severe and prolonged arthritis and reduced ability to clear spirochetes from tissues (22).…”

Section: Discussionmentioning

confidence: 99%

T Cells Exacerbate Lyme Borreliosis in TLR2-Deficient Mice

et al. 2016

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Infection of humans with the spirochete, Borrelia burgdorferi, causes Lyme borreliosis and can lead to clinical manifestations such as arthritis, carditis, and neurological conditions. Experimental infection of mice recapitulates many of these symptoms and serves as a model system for the investigation of disease pathogenesis and immunity. Innate immunity is known to drive the development of Lyme arthritis and carditis, but the mechanisms driving this response remain unclear. Innate immune cells recognize B. burgdorferi surface lipoproteins primarily via toll-like receptor (TLR)2; however, previous work has demonstrated TLR2−/− mice had exacerbated disease and increased bacterial burden. We demonstrate increased CD4 and CD8 T cell infiltrates in B. burgdorferi-infected joints and hearts of C3H TLR2−/− mice. In vivo depletion of either CD4 or CD8 T cells reduced Borrelia-induced joint swelling and lowered tissue spirochete burden, whereas depletion of CD8 T cells alone reduced disease severity scores. Exacerbation of Lyme arthritis correlated with increased production of CXCL9 by synoviocytes, and this was reduced with CD8 T cell depletion. These results demonstrate T cells can exacerbate Lyme disease pathogenesis and prolong disease resolution possibly through dysregulation of inflammatory responses and inhibition of bacterial clearance.

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Section: Discussionmentioning

confidence: 99%

T Cells Exacerbate Lyme Borreliosis in TLR2-Deficient Mice

et al. 2016

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“…Intravital microscopy revealed that Kupffer cells take up spirochetes in the liver, and iNKT cells clustered around them (Lee et al, 2010) presumably carrying out an immune response in the liver sinusoids. These authors also showed that iNKT cell-deficient Jα18 À/À mice have a 25-fold increase in pathogen burden in the joints during this infection (Lee et al, 2010) and that iNKT cells attack the Borrelia spirochetes in the extravascular space (Lee et al, 2014).…”

Section: Borrelia Sppmentioning

confidence: 91%

Activation and Function of iNKT and MAIT Cells

Chandra

Kronenberg

2015

Advances in Immunology

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“…This led to the dampening of whole body inflammation and an increased susceptibility to infection (Wong et al, 2011). Unlike the liver, iNKT cells did not patrol the blood vessels of joints (Lee et al, 2014). Instead, iNKT cells were strategically localized extravascularly along the length of the few blood vessels within the joint (Lee et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Unlike the liver, iNKT cells did not patrol the blood vessels of joints (Lee et al, 2014). Instead, iNKT cells were strategically localized extravascularly along the length of the few blood vessels within the joint (Lee et al, 2014). Upon infection with Borrelia burgdorferi, which adhered to the joint vasculature, iNKT cells were able to recognize and directly kill this pathogen and prevent infection (Lee et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation

et al. 2016

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iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against a variety of bacterial infections including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the potent iNKT cell ligand α-galactosylceramide or during S. pneumoniae infection. In untreated mice the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either α-GalCer or S. pneumoniae, induced CD1d dependent rapid recruitment of neutrophils out of the vasculature. This neutrophil exodus paved the way for extravasation of iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell migration out of the lung vasculature by blocking CCL17 greatly increased susceptibility to S. pneumoniae infection, suggesting a critical role for the secondary wave of iNKT cells in host defense.

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

Cited by 57 publications

References 34 publications

T Cells Exacerbate Lyme Borreliosis in TLR2-Deficient Mice

T Cells Exacerbate Lyme Borreliosis in TLR2-Deficient Mice

Activation and Function of iNKT and MAIT Cells

iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation

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