INTERLEUKIN-4 AND INTERLEUKIN-10 INHIBIT NITRIC OXIDE-DEPENDENT MACROPHAGE KILLING OF CANDIDA-ALBICANS

被引:226
作者
CENCI, E [1 ]
ROMANI, L [1 ]
MENCACCI, A [1 ]
SPACCAPELO, R [1 ]
SCHIAFFELLA, E [1 ]
PUCCETTI, P [1 ]
BISTONI, F [1 ]
机构
[1] UNIV PERUGIA,DEPT EXPTL MED & BIOCHEM SCI,MICROBIOL SECT,VIA GIACHETTO,I-06100 PERUGIA,ITALY
关键词
NITRIC OXIDE; CANDIDA-ALBICANS; INTERLEUKIN-4; INTERLEUKIN-10;
D O I
10.1002/eji.1830230508
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mouse peritoneal and splenic macrophages treated with interferon-gamma (IFN-gamma) and infected with the yeast Candida albicans expressed high fungicidal activity in vitro that correlated with increased nitrite concentrations in culture supernatants. Both effects were reduced by an inhibitor of nitric oxide (NO) synthesis which, in vivo, impaired the animals' ability to mount a footpad reaction and clear the fungus from infected organs. Because T helper type-2 (Th2) cytokines in candidiasis are known to limit the expression of protective Th1 functions, we tested the effect of interleukin (IL)-4 and IL-10 on candidacidal activity and NO production of IFN-gamma-activated macrophages. Fungal killing and NO secretion were inhibited, in a dose-dependent manner, by the two cytokines either separately or in combination. Impaired candidacidal activity was also demonstrable in the presence of monoiodoacetic acid, an inhibitor of phagocytosis. These data demonstrate that NO is involved in macrophage killing of C albicans and support the notion that regulation of Th1 effector function by IL-4 and IL-10 might involve modulation of NO synthesis.
引用
收藏
页码:1034 / 1038
页数:5
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