title: iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation.
abstract: iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against bacterial infections, including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the specific iNKT cell ligand α-galactosylceramide or 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. The neutrophils guided 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 recruitment by blocking CCL17 increased susceptibility to S. pneumoniae infection, suggesting a critical role for the influx of iNKT cells in host defense.
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada; Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Ajitha
authors.initials: A
authors.lastname: Thanabalasuriar
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada; Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Arpan S
authors.initials: AS
authors.lastname: Neupane
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada; Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada; Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: pkubes@ucalgary.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Kubes
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology*