Abstract
Increasing evidence indicates that antibody-dependent cellular cytotoxicity (ADCC) contributes to the control of HIV/SIV infection. However, little is known about the ADCC function of natural killer (NK) cells in non-human primate model. Here we demonstrated that ADCC function of NK cells was significantly compromised in chronic SIV/SHIV infection, correlating closely with the expression of FcγRIIIa receptor (CD16) on NK cells. CD32, another class of IgG Fc receptors, was identified on NK cells with higher expression in the infected macaques and the blockade of CD32 impacted the ability of NK cells to respond to antibody-coated target cells. The inhibition of matrix metalloproteases (MMPs), a group of enzymes normally involved in tissue/receptor remodeling, could restore NK cell-mediated ADCC with increased CD16 expression on macaque NK cells. These data offer a clearer understanding of NK cell-mediated ADCC in rhesus macaques, which will allow us to evaluate the ADCC repertoire arising from preclinical vaccination studies in non-human primates and inform us in the future design of effective HIV vaccination strategies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody-Dependent Cell Cytotoxicity / drug effects
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Antibody-Dependent Cell Cytotoxicity / immunology*
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Cell Line, Tumor
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Chronic Disease
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology
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Humans
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Macaca mulatta
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Matrix Metalloproteinase Inhibitors / pharmacology
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Matrix Metalloproteinases / metabolism
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Mice
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Receptors, IgG / metabolism
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Simian Acquired Immunodeficiency Syndrome / immunology*
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Simian Immunodeficiency Virus / physiology*
Substances
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Matrix Metalloproteinase Inhibitors
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Receptors, IgG
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Matrix Metalloproteinases
Grants and funding
This work was supported by National Major projects for Infectious Diseases Control and Prevention (2012ZX10001008), National Natural Science Foundation of China (81020108030, 31100126), SKLID Development grant (2012SKLID103, 2011SKLID207), Analysis of genetic and immunological background of Macaque Rhesus in China (2012ZX10004501-001-006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.