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 2

AHIV plasma–mediated DC inhibition occurs concurrently with VR.

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AHIV plasma–mediated DC inhibition occurs concurrently with VR. DCs were...
DCs were treated overnight with 10% AHIV, acute HBV, or acute HCV plasma collected at indicated time points before and after VR. DCs were also treated with 10% normal, uninfected donor plasma taken at various time points, generally 2–7 days apart. DCs were then poly I:C stimulated. IL-12p70 levels (as percentages of the levels from uninfected plasma–treated DCs) secreted by DCs treated with plasma from before or after viremia (red line) are graphed versus the plasma viral load (VL) (blue line). The dotted line denotes 100% of control IL-12p70 levels, indicating no inhibition. Arrows indicate start of VR.