Aternatively activated (M2) macrophages display immunomodulatory effects on CD56brigh and CD56dim NK cell effector functions.

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

Buenos Aires

Congreso; IV Latinamerican Society for Immunodeficiencies (LASID) Meeting, LXIII Meeting of the Argentinean Society of Immunology and II French-Argentinean Immunology Meeting.; 2015

Latinamerican Society for Immunodeficiencies (LASID) y Sociedad Argentina de Inmunología (SAI)

Background: Macrophages display a high degree of plasticity. Upon activation, they can become M1 (pro-inflammatory, anti-tumoral) or M2 (anti-inflammatory, pro-tumoral) macrophages. As interaction between M1 and M2 and Natural killer (NK) cells has been poorly explored, the aim of this work was to investigate the consequences of such interaction. Methods: Human monocytes differentiated in vitro to unpolarized macrophages (M0) with M-CSF for 6 days were exposed overnight to LPS and IFN-g or IL-4 to obtain M1 and M2, respectively. NK cells (resting or stimulated with IL-12, IL-15 and IL-18) were co-culture overnight with M1 or M2 and expression of CD69 and CD25, intracellular IFN-g and viability was measured by flow cytometry on CD3-CD56+ cells. Also, degranulation (CD107a expression) was assessed on NK cells after stimulation with K562 cells for 5 h. Results: M1 displayed higher expression of CD86 and CD274 and increased ratio IL-12/IL-10 secretion compared to M0 and M2, while M2 up-regulated CD206 expression. Increased percentages of CD69+ NK cells were observed when resting NK cells were co-cultured with M1 (p<0.01; n=5) compared to NK cells cultured alone or with M2. Lower percentages of CD69+ (p<0.05; n=5) and CD25+ (p<0.001; n=5) NK cells were observed when NK cells were stimulated with cytokines in the presence of M2 compared to M1 or in the absence of macrophages. M2 induced lower percentages of IFN-g+CD56bright cells (p<0.01; n=5) without affecting their viability, and less degranulation of CD56dim cells (p<0.01; n=5) than M1. Conclusion: M2 negatively regulate NK cell activation and effector functions.