The interaction of alternatively activated (M2) macrophages and NK cells result in a negative modulation of NK cell activation and effector functions

NÚÑEZ, SOL YANEL; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; DOMAICA, CAROLINA INÉS; ARAYA, ROMINA ELIZABETH; SIERRA, JESSICA MARIEL; ZWIRNER, NORBERTO WALTER; TORRES, NICOLÁS IGNACIO; ZIBLAT, ANDREA; FUERTES, MERCEDES BEATRIZ

Melbourne

Congreso; ICI2016. International Congress of Immunology; 2016

International Union of Immunological Societies (IUIS)

Macrophages display a highdegree of plasticity. Upon activation, they can become pro-inflammatory (M1) oranti-inflammatory (M2) macrophages. As interaction between M2 and Naturalkiller (NK) cells has been poorly explored, the aim of this work was toinvestigate the consequences of such interaction. Human monocytesdifferentiated in vitro to unpolarized macrophages (M0) with M-CSF for 6 dayswere exposed overnight to LPS and IFN-gor IL-4 to obtain M1 and M2, respectively. M1displayed higher expression of CD86 and CD274 and increased IL-12 secretioncompared to M0 and M2, while M2 up-regulated CD206 expression. NK cells(resting or stimulated with IL-12, IL-15 and IL-18) were co-culture overnightwith M1 or M2 and expression of CD69 and CD25, intracellular IFN-gand viability was measured by flow cytometry on CD3-CD56+cells. Also, degranulation was assessed on NK cells after stimulationwith K562 cells for 5 h. Increased percentages of CD69+ NK cellswere observed when resting NK cells were co-cultured with M1 compared to NKcells cultured alone or with M2. Significantly lower percentages of CD25+were observed in CD56dim and CD56bright NK cells stimulatedwith cytokines in the presence of M2 compared to M1 or in the absence ofmacrophages, while lower percentages of CD69+ NK cells were observed onlyin the CD56bright subpopulation (p<0.001). Moreover, M2 induced lower percentages of IFN-g+CD56bright cells (p<0.001) and less degranulation of CD56dim cells (p<0.01)than M1, without affecting their viability. Thus, M2negatively regulate NK cell activation and effector functions.