title: FcγRIII (CD16)-mediated ADCC by NK cells is regulated by monocytes and FcγRII (CD32).
abstract: 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.
authors.affiliation: Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Nupur
authors.initials: N
authors.lastname: Bhatnagar
authors.forename: Fareed
authors.initials: F
authors.lastname: Ahmad
authors.forename: Henoch S
authors.initials: HS
authors.lastname: Hong
authors.forename: Johanna
authors.initials: J
authors.lastname: Eberhard
authors.forename: I-Na
authors.initials: IN
authors.lastname: Lu
authors.forename: Matthias
authors.initials: M
authors.lastname: Ballmaier
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Roland
authors.initials: R
authors.lastname: Jacobs
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer-Olson
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: C499173:FCGR2B protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG
keywords: ADCC; Fcγ receptors; Monocytes; NK cells