title: Evidence of dysregulation of dendritic cells in primary HIV infection.
abstract: Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both innate and adaptive immunity against pathogens such as HIV. During the course of HIV infection, blood DC numbers fall substantially. In the present study, we sought to determine how early in HIV infection the reduction occurs and whether the remaining DC subsets maintain functional capacity. We find that both myeloid DC and plasmacytoid DC levels decline very early during acute HIV infection. Despite the initial reduction in numbers, those DCs that remain in circulation retain their function and are able to stimulate allogeneic T-cell responses, and up-regulate maturation markers plus produce cytokines/chemokines in response to stimulation with TLR7/8 agonists. Notably, DCs from HIV-infected subjects produced significantly higher levels of cytokines/chemokines in response to stimulation with TLR7/8 agonists than DCs from uninfected controls. Further examination of gene expression profiles indicated in vivo activation, either directly or indirectly, of DCs during HIV infection. Taken together, our data demonstrate that despite the reduction in circulating DC numbers, those that remain in the blood display hyperfunctionality and implicates a possible role for DCs in promoting chronic immune activation.
authors.affiliation: New York University, School of Medicine, Cancer Institute, New York, NY, USA.
authors.forename: Rachel Lubong
authors.initials: RL
authors.lastname: Sabado
authors.forename: Meagan
authors.initials: M
authors.lastname: O'Brien
authors.forename: Abhignya
authors.initials: A
authors.lastname: Subedi
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Taylor
authors.forename: Oliver
authors.initials: O
authors.lastname: Dibben
authors.forename: Andrea
authors.initials: A
authors.lastname: Stacey
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Frederick
authors.initials: F
authors.lastname: Siegal
authors.forename: Michael
authors.initials: M
authors.lastname: Shodell
authors.forename: Kokila
authors.initials: K
authors.lastname: Shah
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lifson
authors.forename: Arthur
authors.initials: A
authors.lastname: Nadas
authors.forename: Michael
authors.initials: M
authors.lastname: Marmor
authors.forename: Richard
authors.initials: R
authors.lastname: Hutt
authors.forename: David
authors.initials: D
authors.lastname: Margolis
authors.forename: Donald
authors.initials: D
authors.lastname: Garmon
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
authors.forename: Fred
authors.initials: F
authors.lastname: Valentine
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
mesh_terms: D001772:Blood Cell Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D015870:Gene Expression; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D015398:Signal Transduction; D013997:Time Factors; D051193:Toll-Like Receptors / Q000819:agonists; D019562:Viral Load
chemical_list: D018925:Chemokines; D016207:Cytokines; D051193:Toll-Like Receptors