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

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 1

AHIV plasma inhibits TLR-stimulated DC function.

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AHIV plasma inhibits TLR-stimulated DC function. (A) DCs were treated ov...
(A) DCs were treated overnight with 10% uninfected donor plasma or plasma taken from patients with AHIV during Fiebig stages 1 and 2. The next day, DCs were stimulated with the TLR3 agonist poly I:C, and cytokine production was analyzed the following day. Mean is shown by horizontal bars, with each dot representing individual plasma samples. (B) DCs were tested as described in A with AHIV plasma (Fiebig stages 1 and 2), including seroconversion panels obtained from ZeptoMetrix Corp. (black bars), University of North Carolina Center for Infectious Diseases (white bar), Duke University Medical Center (light gray bar), Queen Elizabeth Central Hospital (medium gray bars), and Lilongwe Central Hospital (dark gray bars). The level of IL-12p70 production of AHIV plasma–treated DCs is shown, expressed as a percentage of the IL-12p70 levels produced by uninfected donor plasma–treated DCs (100% represents no inhibition). This figure combines multiple experiments compared against multiple uninfected control donor plasma samples (ranging from n = 12 to n = 50). (C) DCs were treated with plasma as described in A. DCs were then stimulated with poly I:C, washed, and cocultured with allogeneic naive CD4+ T cells. T cell cytokine production was analyzed at day 6. Mean is shown by horizontal bars, with each dot representing individual plasma samples. (D) DCs were treated as described in C and then cocultured with NK cells. NK cell cytokine production was analyzed the next day. Representative experiments are shown.