title: Immediate T-Helper 17 Polarization Upon Triggering CD11b/c on HIV-Exposed Dendritic Cells.
abstract: Early on in human immunodeficiency virus (HIV) type 1 infection, gut T-helper (Th) 17 cells are massively depleted leading eventually to compromised intestinal barrier function and excessive immune activation. In contrast, the functional Th17 cell compartment of the gut is well-maintained in nonpathogenic simian immunodeficiency virus infection as well as HIV-1 long-term nonprogressors. Here, we show that dendritic cells (DCs) loaded with HIV-1 bearing high surface complement levels after incubation in plasma from HIV-infected individuals secreted significantly higher concentrations of Th17-polarizing cytokines than DCs exposed to nonopsonized HIV-1. The enhanced Th17-polarizing capacity of in vitro-generated and BDCA-1(+) DCs directly isolated from blood was linked to activation of ERK. In addition, C3a produced from DCs exposed to complement-opsonized HIV was associated with the higher Th17 polarization. Our in vitro and ex vivo data, therefore, indicate that complement opsonization of HIV-1 strengthens DC-mediated antiviral immune functions by simultaneously triggering Th17 expansion and intrinsic C3 formation via DC activation.
authors.affiliation: Division of Hygiene and Medical Microbiology.
authors.forename: Doris
authors.initials: D
authors.lastname: Wilflingseder
authors.affiliation: Department of Internal Medicine VI, Clinical Immunology and Infectious Diseases.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schroll
authors.affiliation: Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Hackl
authors.affiliation: Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gallasch
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge University College London, Windeyer Institute, United Kingdom.
authors.forename: Dan
authors.initials: D
authors.lastname: Frampton
authors.affiliation: Division of Hygiene and Medical Microbiology.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.affiliation: Unité de Régulation des Infections Rétrovirales.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
authors.affiliation: Unité HIV Inflammation et Persistance, Institut Pasteur.
authors.forename: Asier
authors.initials: A
authors.lastname: Saez-Cirion
authors.affiliation: INSERM U1012, Régulation de la Réponse Immune, Infection VIH1 et Autoimmunité, Université Paris Sud APHP, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.affiliation: Unité de Régulation des Infections Rétrovirales APHP Hôpital Européen Georges Pompidou, Paris.
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge University College London, Windeyer Institute, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
authors.affiliation: Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Austria.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Teunis
authors.initials: T
authors.lastname: Geijtenbeek
authors.affiliation: Department of Internal Medicine VI, Clinical Immunology and Infectious Diseases.
authors.forename: Günter
authors.initials: G
authors.lastname: Weiss
authors.affiliation: Division of Hygiene and Medical Microbiology.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Posch
mesh_terms: D000328:Adult; D039481:CD11b Antigen / Q000032:analysis*; D039521:CD11c Antigen / Q000032:analysis*; D002454:Cell Differentiation; D003165:Complement System Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058504:Th17 Cells / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; C509295:ITGAM protein, human; D003165:Complement System Proteins
keywords: HIV-1; MAPK; Th17; complement; dendritic cells; opsonization