title: CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type 1 immunity.
abstract: The ability of dendritic cells (DC) to mediate CD4(+) T cell help for cellular immunity is guided by instructive signals received during DC maturation, as well as the resulting pattern of DC responsiveness to the Th signal, CD40L. Furthermore, the professional transfer of antigenic information from migratory DC to lymph node-residing DC is critical for the effective induction of cellular immune responses. In this study we report that, in addition to their enhanced IL-12p70 producing capacity, human DC matured in the presence of inflammatory mediators of type 1 immunity are uniquely programmed to form networks of tunneling nanotube-like structures in response to CD40L-expressing Th cells or rCD40L. This immunologic process of DC reticulation facilitates intercellular trafficking of endosome-associated vesicles and Ag, but also pathogens such HIV-1, and is regulated by the opposing roles of IFN-γ and IL-4. The initiation of DC reticulation represents a novel helper function of CD40L and a superior mechanism of intercellular communication possessed by type 1 polarized DC, as well as a target for exploitation by pathogens to enhance direct cell-to-cell spread.
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Colleen R
authors.identifier: http://orcid.org/0000-0003-0977-2990
authors.initials: CR
authors.lastname: Zaccard
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261; and.
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Fecek
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Aarika L
authors.initials: AL
authors.lastname: Yates
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Russell D
authors.initials: RD
authors.lastname: Salter
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Velpandi
authors.initials: V
authors.lastname: Ayyavoo
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261; rbm19@pitt.edu.
authors.forename: Robbie B
authors.initials: RB
authors.lastname: Mailliard
mesh_terms: D001692:Biological Transport; D023201:CD40 Ligand / Q000378:metabolism* / Q000494:pharmacology; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D023201:CD40 Ligand