Immediate T-Helper 17 Polarization Upon Triggering CD11b/c on HIV-Exposed Dendritic Cells

Doris Wilflingseder (1) , Andrea Schroll (1) , Hubert Hackl (1) , Ralf Gallasch (1) , Dan Frampton (2, 3) , Cornelia Lass-Flörl (1) , Gianfranco Pancino (4) , Zlatko Trajanoski (5) , Asier Saez-Cirion (6) , Olivier Lambotte (7, 8, 9) , Laurence Weiss (10, 4) , Paul Kellam (3, 2) , Teunis Geijtenbeek (5) , Günter Weiss (1) , Wilfried Posch (1)

1 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
2 UCL - University College of London [London]
3 Wellcome Trust Genome Campus
4 Régulation des Infections Rétrovirales
5 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
6 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
7 Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre]
8 UP11 UFR Médecine - Université Paris-Sud - Paris 11 - Faculté de médecine
9 Régulation de la réponse immune, infection VIH-1 et autoimmunité
10 HEGP - Hôpital Européen Georges Pompidou [APHP]

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.

Mots clés: Adult; Antigens; CD11b; CD11c; Cell Differentiation; complement; Complement System Proteins; Dendritic Cells; Female; HIV-1; Humans; Male; MAPK; Middle Aged; opsonization; Th17; Th17 Cells

Domaines: Immunologie

Doris Wilflingseder, Andrea Schroll, Hubert Hackl, Ralf Gallasch, Dan Frampton, et al.. Immediate T-Helper 17 Polarization Upon Triggering CD11b/c on HIV-Exposed Dendritic Cells. Journal of Infectious Diseases, 2015, 212 (1), pp.44--56. ⟨10.1093/infdis/jiv014⟩. ⟨pasteur-01420413⟩