HIV-1 infection–induced apoptotic microparticles inhibit human DCs via CD44
Davor Frleta, … , Barton F. Haynes, Nina Bhardwaj
Davor Frleta, … , Barton F. Haynes, Nina Bhardwaj
Published November 19, 2012
Citation Information: J Clin Invest. 2012;122(12):4685-4697. https://doi.org/10.1172/JCI64439.
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Research Article AIDS/HIV Article has an altmetric score of 13

HIV-1 infection–induced apoptotic microparticles inhibit human DCs via CD44

Abstract

Acute HIV-1 infection results in dysregulated immunity, which contributes to poor control of viral infection. DCs are key regulators of both adaptive and innate immune responses needed for controlling HIV-1, and we surmised that factors elicited during acute HIV-1 infection might impede DC function. We derived immature DCs from healthy donor peripheral blood monocytes and treated them with plasma from uninfected control donors and donors with acute HIV-1 infections. We found that the plasma from patients with HIV specifically inhibited DC function. This suppression was mediated by elevated apoptotic microparticles derived from dying cells during acute HIV-1 infection. Apoptotic microparticles bound to and inhibited DCs through the hyaluronate receptor CD44. These data suggest that targeting this CD44-mediated inhibition by apoptotic microparticles could be a novel strategy to potentiate DC activation of HIV-specific immunity.

Authors

Davor Frleta, Carolyn E. Ochoa, Holger B. Kramer, Shaukat Ali Khan, Andrea R. Stacey, Persephone Borrow, Benedikt M. Kessler, Barton F. Haynes, Nina Bhardwaj

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Figure 4

Apoptotic MPs inhibit TLR-stimulated DC function.

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Apoptotic MPs inhibit TLR-stimulated DC function. (A) DCs were treated o...
(A) DCs were treated overnight with apoptotic MPs (Apo-MP), control MPs (Cont-MP), or no MPs. DCs were subsequently poly I:C stimulated, and cytokine production was analyzed. (B) DCs were treated with MPs as described in A. DCs were then stimulated with 100 ng/ml flagellin, and IL-6 production was measured (flagellin-stimulated DCs do not produce substantial IL-12p70). (C) DCs were treated with MPs as described in A. After being poly I:C stimulated for 4 to 6 hours, DCs were washed, cocultured with isolated allogeneic naive CD4+ T cells or (D) naive CD8+ T cells for 6 days, and T cell cytokine production was assessed. (E) DCs were treated with MPs and stimulated as described in C. DCs were then cocultured overnight with isolated NK cells, and NK cell cytokine production was assessed. Data are representative of at least 3 independent experiments. The P values (unpaired Student’s t test) for indicated comparisons are shown. (F) DCs were treated with MPs derived from AHIV plasma from indicated donors. DCs were then poly I:C stimulated and IL-12p70 levels were analyzed. IL-12p70 levels were normalized to levels from DCs treated with MPs derived from uninfected plasma (at least 2 different control donors per experiment). The dotted line denotes 100% of control levels, indicating no inhibition.