Graphene oxide nanosheets increase Candida albicans killing by pro-inflammatory and reparative peritoneal macrophages

被引:24
作者
Diez-Orejas, Rosalia [1 ]
Jose Feito, Maria [2 ]
Cicuendez, Monica [3 ,4 ]
Casarrubios, Laura [2 ]
Maria Rojo, Jose [5 ]
Teresa Portoles, Maria [2 ]
机构
[1] Univ Complutense Madrid, Fac Pharm, Dept Microbiol & Parasitol, E-28040 Madrid, Spain
[2] Univ Complutense Madrid, Fac Pharm, Dept Biochem & Mol Biol, Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, E-28040 Madrid, Spain
[3] Univ Aveiro, Dept Chem, CIGECO Aveiro Inst Mat, Campus Univ Santiago, P-3810193 Aveiro, Portugal
[4] Univ Aveiro, Mech Engn Dept, TEMA Nanotechnol Grp, Campus Univ Santiago, P-3810193 Aveiro, Portugal
[5] CSIC, Ctr Invest Biol, Dept Mol Biomed, Madrid 28040, Spain
关键词
Graphene oxide; Macrophage; Candida albicans; Phagocytosis; CFU inhibition; Nanomaterial; INTERFERON-GAMMA; HOST-DEFENSE; NANOPARTICLES; POLARIZATION; PHAGOCYTOSIS; EXOCYTOSIS; PLASTICITY; MECHANISMS; RESISTANCE; DELIVERY;
D O I
10.1016/j.colsurfb.2018.07.027
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Graphene oxide (GO) is a new nanomaterial with different potential biomedical applications due to its excellent physicochemical properties and ease of surface functionalization. Macrophages play key roles in the control of fungal infections preventing invasive candidiasis by both limiting the growth of the opportunistic fungal pathogen Candida albicans and activating other immune effector cells. In order to know if macrophages maintain their immunocompetence against this microorganism after GO uptake, we have evaluated the interactions at the interface of GO nanosheets, macrophages and Candida albicans. Poly (ethylene glycol-amine)-derivatized GO nanosheets labelled with fluorescein isothiocyanate (FITC-PEG-GO), were efficiently taken up by peritoneal macrophages inducing a significant increase of C. albicans phagocytosis by both pro-inflammatory macrophages (M1/stimulated with LPS/IFN-gamma) and reparative macrophages (M2/stimulated with IL-4). On the other hand, after FITC-PEG-GO treatment and C. albicans infection, the percentages of GO(+) macrophages diminished when Candida uptake increased in every condition (macrophages with no stimuli, M1 and M2 macrophages), thus suggesting the exocytosis of this nanomaterial as a dynamic mechanism favoring fungal phagocytosis. For the first time, we have analyzed the effects of PEG-GO nanosheets on Candida albicans killing by unstimulated, M1 and M2 macrophages, evidencing that intracellular GO modulates the macrophage candidacidal activity in a multiplicity of infection (MOI) dependent manner. At MOI 1, the high intracellular GO levels increase the fungicidal activity of basal and stimulated macrophages. At MOI 5, as intracellular GO decreases, the previous pro-inflammatory or reparative stimulus predefines the killing ability of macrophages. In summary, GO treatment enhances classical M1 macrophage activation, important for pathogen eradication, and diminishes alternative activation of M2 macrophages, thus decreasing fungal persistence and avoiding chronic infectious diseases.
引用
收藏
页码:250 / 259
页数:10
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