Differential susceptibility to human immunodeficiency virus type 1 infection of myeloid and plasmacytoid dendritic cells.
Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) plays an important role in HIV-1 transmission and pathogenesis. Here, we studied the susceptibility of ex vivo-isolated CD11c+ myeloid DCs (MDCs) and CD123+ plasmacytoid DCs (PDCs) to HIV-1 infection and the function of these cells early after infection. Both DC subsets were susceptible to CCR5- and CXCR4-using HIV-1 isolates (BaL and IIIB, respectively). However, MDCs were more susceptible to HIV-1(BaL) infection than donor-matched PDCs. In addition, HIV-1(BaL) infected MDCs more efficiently than HIV-1(IIIB), whereas PDCs were equally susceptible to both isolates. While exposure to HIV-1 alone resulted in only weak maturation of DCs, Toll-like receptor 7/8 ligation induced full maturation in both infected and uninfected DCs. Maturation did not increase HIV-1 replication in infected DCs, and infected DCs retained their ability to produce tumor necrosis factor alpha after stimulation. Both HIV-1 isolates induced alpha interferon production exclusively in PDCs, irrespective of productive infection. In conclusion, PDCs and MDCs were susceptible to HIV-1 infection, but neither displayed functional defects as a consequence of infection. The difference in susceptibility of PDCs and MDCs to HIV-1 may have implications for HIV-1 transmission and DC-mediated transfer of HIV-1 to T cells.
Smed-Sörensen
Anna
A
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, F59 Huddinge University Hospital, S-141 86 Stockholm, Sweden. Anna.Smed.Sorensen@medhs.ki.se
Loré
Karin
K
Vasudevan
Jayanand
J
Louder
Mark K
MK
Andersson
Jan
J
Mascola
John R
JR
Spetz
Anna-Lena
AL
Koup
Richard A
RA
D003713:Dendritic Cells / Q000821:virology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis; D022423:Myeloid Cells / Q000166:cytology / Q000821:virology*; D010950:Plasma Cells / Q000166:cytology / Q000821:virology*; D021122:Protein Subunits / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016655:HIV Core Protein p24; D007093:Imidazoles; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C402365:resiquimod