FcγRIII (CD16)-mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32)
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FcγRIII (CD16)-mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32). / Bhatnagar, Nupur; Ahmad, Fareed; Hong, Henoch S; Eberhard, Johanna; Lu, I-Na; Ballmaier, Matthias; Schmidt, Reinhold E; Jacobs, Roland; Meyer-Olson, Dirk.
in: EUR J IMMUNOL, Jahrgang 44, Nr. 11, 11.2014, S. 3368-79.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - FcγRIII (CD16)-mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32)
AU - Bhatnagar, Nupur
AU - Ahmad, Fareed
AU - Hong, Henoch S
AU - Eberhard, Johanna
AU - Lu, I-Na
AU - Ballmaier, Matthias
AU - Schmidt, Reinhold E
AU - Jacobs, Roland
AU - Meyer-Olson, Dirk
N1 - © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2014/11
Y1 - 2014/11
N2 - Monocytes are known to engage in reciprocal crosstalk with NK cells but their influence on NK-cell-associated antibody-dependent cellular cytotoxicity (ADCC) is not well understood. We demonstrate that in humans FcγRIII (CD16)-dependent ADCC by NK cells is considerably enhanced by monocytes, and that this effect is regulated by FcγRII (CD32) crosslinking in healthy individuals. It is known that during HIV-1 infection, NK cells are known to express low levels of CD16 and exhibit reduced ADCC. We show that immune regulation of CD16-mediated NK-cell cytotoxicity by monocytes through CD32 engagement is substantially disturbed in chronic progressive HIV-1 infection. Expression of activating isoform of CD32 represented a compensatory mechanism for reduced expression of CD16 on NK cells during HIV-1 infection. As a result, the regulation of NK-cell-associated ADCC by monocytes is skewed and eventually constitutes a novel factor that contributes to HIV-1-associated immune deficiency, dysregulation and pathogenesis. Our data therefore provide evidence, for the first time, that in humans monocytes act as a rheostat for FcγRIII-mediated NK-cell functions maintaining a well-balanced immune response.
AB - Monocytes are known to engage in reciprocal crosstalk with NK cells but their influence on NK-cell-associated antibody-dependent cellular cytotoxicity (ADCC) is not well understood. We demonstrate that in humans FcγRIII (CD16)-dependent ADCC by NK cells is considerably enhanced by monocytes, and that this effect is regulated by FcγRII (CD32) crosslinking in healthy individuals. It is known that during HIV-1 infection, NK cells are known to express low levels of CD16 and exhibit reduced ADCC. We show that immune regulation of CD16-mediated NK-cell cytotoxicity by monocytes through CD32 engagement is substantially disturbed in chronic progressive HIV-1 infection. Expression of activating isoform of CD32 represented a compensatory mechanism for reduced expression of CD16 on NK cells during HIV-1 infection. As a result, the regulation of NK-cell-associated ADCC by monocytes is skewed and eventually constitutes a novel factor that contributes to HIV-1-associated immune deficiency, dysregulation and pathogenesis. Our data therefore provide evidence, for the first time, that in humans monocytes act as a rheostat for FcγRIII-mediated NK-cell functions maintaining a well-balanced immune response.
KW - Antibody-Dependent Cell Cytotoxicity/immunology
KW - GPI-Linked Proteins/biosynthesis
KW - HIV Infections/immunology
KW - HIV-1/immunology
KW - Humans
KW - Killer Cells, Natural/immunology
KW - Monocytes/immunology
KW - Receptors, IgG/biosynthesis
U2 - 10.1002/eji.201444515
DO - 10.1002/eji.201444515
M3 - SCORING: Journal article
C2 - 25100508
VL - 44
SP - 3368
EP - 3379
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 11
ER -
