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. 2011 Jul 5;415(2):160-7.
doi: 10.1016/j.virol.2011.03.012. Epub 2011 May 12.

Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals

Anne-Sophie Dugast  1 , Andrew Tonelli, Christoph T Berger, Margaret E Ackerman, Gaia Sciaranghella, Qingquan Liu, Magdalena Sips, Ildiko Toth, Alicja Piechocka-Trocha, Musie Ghebremichael, Galit Alter
Affiliations

Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals

Anne-Sophie Dugast et al. Virology. .

Abstract

In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection.

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Conflict of interest statement

Potential conflict of interest: none reported

Figures

FIG. 1
FIG. 1. Acute HIV-1 infection is associated with changes in FcγRI expression on mDCs and monocytes
The dot plots depict changes in the frequency (A) and intensity (B) of FcγRI (CD64) expression on (i) mDCs, (ii) pDCs and (iii) monocytes derived from acute (●), chronic treated (■), chronic untreated (⬪), controllers (⬧) and HIV-1 negative controls (◆).
FIG. 2
FIG. 2. FcγRII expression is strongly downregulated in chronic HIV infection
The frequency (A) and the intensity (B) of FcγRII (CD32) expression was compared among acute (●), chronic treated (■), chronic untreated (⬪), controllers (⬧) and HIV-1 negative controls (◆) on (i) mDCs, (ii) pDCs and (iii) monocytes.
FIG. 3
FIG. 3. FcγRIIIa expression is downregulated on mDC and monocytes in chronic HIV-1 infection
The frequency (A) of FcγRIII+ cells and the expression (B) of FcγRIII on mDCs, pDCs and monocytes was compared in subjects in HIV-infected subjects in acute (●), chronic treated ■), chronic untreated (⬪), controllers (⬧) and HIV-1 negative controls (◆).
FIG. 4
FIG. 4. Elevated frequencies of FcεR+ monocytes in acute HIV-1 infection
The percentage and intensity FcεR (CD23) (A, B) and FcαR (CD89) (C, D) was compared on mDCs, pDCs and monocytes derived from patients at different stages of the infection including cells derived from acute (●), chronic treated (■), chronic untreated (⬪), controllers (⬧) and HIV-1 negative controls (◆).
FIG. 5
FIG. 5. Impact of FcγRI, FcγRII and FcγRIIIa expression in FcR-mediated phagocytosis
The dot plots represent differences in FcR mediated phagocytosis, measured as the proportion of phagocytic cells that have taken up an antibody coated target cell (A) or the intensity of phagocytosis (B), in mDCs (FIG. 5i) and monocytes (FIG. 5ii) among a sub-group of acutely infected patients, chronic treated, chronic untreated, controllers and HIV-1 negative individuals. (C) The bars represent the percentage of reduction in phagocytosis in mDCs (i) or monocytes (ii) in 3 different donors in the presence of FcγR-blocking antibodies.
See this image and copyright information in PMC

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