title: TLR-exosomes exhibit distinct kinetics and effector function.
abstract: The innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. Here we show that exosomes from TLR stimulated cells can largely recapitulate TLR activation in distal cells in vitro. We can abrogate the action-at-a-distance signaling of exosomes by UV irradiation, demonstrating that RNA is crucial for their effector function. We are the first to show that exosomes derived from poly(I:C) stimulated cells induce in vivo macrophage M1-like polarization within murine lymph nodes. These poly(I:C) exosomes demonstrate enhanced trafficking to the node and preferentially recruit neutrophils as compared to control exosomes. This work definitively establishes the differential effector function for exosomes in communicating the TLR activation state of the cell of origin.
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.|Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology, USA.
authors.forename: Swetha
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Su
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Shashidhar
authors.initials: S
authors.lastname: Ravishankar
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Moore
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: PamelaSara
authors.initials: P
authors.lastname: Head
authors.affiliation: Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology, USA.|Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, USA.
authors.forename: J Brandon
authors.initials: JB
authors.lastname: Dixon
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.|Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology, USA.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Vannberg
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011070:Poly I-C; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D011070:Poly I-C