title: Human iNKT Cells Promote Protective Inflammation by Inducing Oscillating Purinergic Signaling in Monocyte-Derived DCs.
abstract: Invariant natural killer T (iNKT) cells are innate T lymphocytes that promote host defense against a variety of microbial pathogens. Whether microbial ligands are required for their protective effects remains unclear. Here, we show that iNKT cells stimulate human-monocyte-derived dendritic cells (DCs) to produce inflammatory mediators in a manner that does not require the presence of microbial compounds. Interleukin 2 (IL-2)-exposed iNKT cells selectively induced repeated cytoplasmic Ca(2+) fluxes in DCs that were dependent on signaling by the P2X7 purinergic receptor and mediated by ATP released during iNKT-DC interactions. Exposure to iNKT cells led to DC cyclooxygenase 2 (PTGS2) gene transcription, and release of PGE2 that was associated with vascular permeabilization in vivo. Additionally, soluble factors were released that induced neutrophil recruitment and activation and enhanced control of Candida albicans. These results suggest that sterile interactions between iNKT cells and monocyte-derived DCs lead to the production of non-redundant inflammatory mediators that promote neutrophil responses.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: Xuequn
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: Ginger M
authors.initials: GM
authors.lastname: Pocock
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: Akshat
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Peery
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Fites
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Felley
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Zarnowski
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Stewart
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Erwin
authors.initials: E
authors.lastname: Berthier
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Klein
authors.affiliation: Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Sherer
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA. Electronic address: jegumperz@wisc.edu.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gumperz
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7