M2 macrophages limit NK cell-mediated cytotoxicity and IFN-gamma; secretion through different mechanisms

SOL YANEL NUÑEZ; ANDREA ZIBLAT; FLORENCIA SECCHIARI; NICOLAS I. TORRES; JESSICA MARIEL SIERRA; XIMENA LUCIA RAFFO; ROMINA ELIZABETH ARAYA; CAROLINA INES DOMAICA; MERCEDES BEATRIZ FUERTES; NORBERTO WALTER ZWIRNER

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2018

0022-1767

Upon activation, macrophages can become pro-inflammatory (M1) or anti-inflammatory (M2) cells. Moreover, NK cells are critical players during immunity against tumors. As the outcome of the crosstalk between M2 and NK cells remains ill-defined, we interrogated the consequencesof such interaction using resting or cytokine-stimulated human NK cells co-cultured with M1 or M2. We observed a lower percentage of activated NK cells that produced less IFN-gamma upon coculture with M2. Also, CD56dim cells co-cultured with M2 displayed lower degranulation and cytotoxic activity than NK cells co-cultured with M1. Soluble TGF-β accounted for the diminished IFN-gamma production by CD56bright NK cells, while M2-driven contact-dependent up-regulation of CD85j (ILT-2) on CD56dim NK cells accounted for the generation of hyporesponsive NK cells with limited degranulation capacity, even in the absence of M2. Thus, M2 restrain NK cell activation and effector functions through different mechanisms that constrain IFN-gamma production and cytotoxicity. These results unravel an inhibitory circuit of possible relevance in pathological situations