Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur J Immunol. 2011 Oct;41(10):2915-24. doi: 10.1002/eji.201141418. Epub 2011 Aug 30.
In the present study, we investigated the functional differences between cluster of differentiation (CD)14(++) CD16(-) and CD14(+) CD16(+) monocytes during anti-Candida host defense. CD14(++) CD16(-) are the "classical" monocytes and represent the majority of circulating monocytes in humans, while CD14(+) CD16(+) monocytes patrol the vasculature for maintenance of tissue integrity and repair. Both monocyte subsets inhibited the germination of live Candida albicans, and there was no difference in their capacity to phagocytose and kill Candida. Although production of IL-6 and IL-10 induced by C. albicans was found to be similar between monocyte subsets, IL-1β and prostaglandin E2 (PGE2) production was higher in CD14(++) CD16(-) compared with CD14(+) CD16(+) monocytes. In line with the increased production of IL-1β and PGE2, central mediators for inducing Th17 responses, CD14(++) CD16(-) monocytes induced greater Th17 responses upon stimulation with heat-killed C. albicans yeast. The percentage of cells that expressed mannose receptor (MR) was higher in the CD14(++) CD16(-) monocyte subset, and MR-specific stimulation induced higher Th17 responses only in co-cultures of CD14(++) CD16(-) monocytes and CD4 lymphocytes. In conclusion, both monocyte subsets have potent innate antifungal properties, but only CD14(++) CD16(-) monocytes are capable of inducing a potent Th17 response to C. albicans, an important component of antifungal host defense.
在本研究中，我们研究了分化群（CD）14（++）CD16（-）和 CD14（+）CD16（+）单核细胞在抗念珠菌宿主防御中的功能差异。CD14（++）CD16（-）是“经典”单核细胞，代表人类循环单核细胞的大多数，而 CD14（+）CD16（+）单核细胞则在血管中巡逻，以维持组织完整性和修复。两种单核细胞亚群均抑制活白色念珠菌的发芽，并且吞噬和杀死白色念珠菌的能力没有差异。尽管发现两种单核细胞亚群对白色念珠菌诱导的 IL-6 和 IL-10 的产生相似，但 CD14（++）CD16（-）单核细胞产生的 IL-1β 和前列腺素 E2（PGE2）高于 CD14（+）CD16（+）单核细胞。与增加的 IL-1β 和 PGE2 一致，这是诱导 Th17 反应的中心介质，与热杀死的白色念珠菌酵母刺激相比，CD14（++）CD16（-）单核细胞诱导更强的 Th17 反应。甘露糖受体（MR）表达细胞的百分比在 CD14（++）CD16（-）单核细胞亚群中更高，并且仅在 CD14（++）CD16（-）单核细胞和 CD4 淋巴细胞的共培养物中，MR 特异性刺激才会诱导更高的 Th17 反应。总之，两种单核细胞亚群均具有强大的先天抗真菌特性，但只有 CD14（++）CD16（-）单核细胞才能诱导对白色念珠菌的强烈 Th17 反应，这是抗真菌宿主防御的重要组成部分。
