Evidence of dysregulation of dendritic cells in primary HIV infection.
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.
Sabado
Rachel Lubong
RL
New York University, School of Medicine, Cancer Institute, New York, NY, USA.
O'Brien
Meagan
M
Subedi
Abhignya
A
Qin
Li
L
Hu
Nan
N
Taylor
Elizabeth
E
Dibben
Oliver
O
Stacey
Andrea
A
Fellay
Jacques
J
Shianna
Kevin V
KV
Siegal
Frederick
F
Shodell
Michael
M
Shah
Kokila
K
Larsson
Marie
M
Lifson
Jeffrey
J
Nadas
Arthur
A
Marmor
Michael
M
Hutt
Richard
R
Margolis
David
D
Garmon
Donald
D
Markowitz
Martin
M
Valentine
Fred
F
Borrow
Persephone
P
Bhardwaj
Nina
N
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
D018925:Chemokines; D016207:Cytokines; D051193:Toll-Like Receptors