Xiaoxiao Wan, Sibiao Yue, Xiaopeng Xiong, Ping Zheng, Gang Chen
Department of Urology, Jinshan Hospital, Fudan University, Shanghai, China.
Immunol Invest. 2007;36(3):337-50. doi: 10.1080/08820130601109719.
Th1-type immune cytokines are essential to establish adaptive immunity against various microbial pathogens, including Escherichia coli, which cause most urinary tract infections (UTIs). Dendritic cells (DCs) are vital to initiate Th1 immunity, while neutrophils, also referred to here as polymorphonuclear leukocytes (PMN) are reported to be involved in Th1 immunity initiation by secreting several chemokines and cytokines. We found that lipopolysaccharide (LPS)-triggered PMN (LPS-PMN) in vitro induced strong up-regulation of DCs surface markers CD40, CD80, MHC-II (Iab), and CD86 either by secreting soluble factors, such as TNF-alpha, or by PMN-DC cellular contact. LPS-PMN also stimulated DCs to produce IL-12 and TNF-alpha. Furthermore, purified DCs activated by LPS-PMN were able to present specific antigen to T cells and drive Th1 differentiation by producing large amount of IFN-gamma but low amount of IL-4. Our results suggest a regulatory role of PMN for DCs function in adaptive immune responses, thereby providing a link between innate and adaptive immunity.
1型辅助性T细胞(Th1)免疫细胞因子对于建立针对各种微生物病原体的适应性免疫至关重要,这些病原体包括导致大多数尿路感染(UTI)的大肠杆菌。树突状细胞(DC)对于启动Th1免疫至关重要,而中性粒细胞(本文中也称为多形核白细胞(PMN))据报道通过分泌多种趋化因子和细胞因子参与Th1免疫的启动。我们发现,体外脂多糖(LPS)刺激的PMN(LPS-PMN)通过分泌可溶性因子(如肿瘤坏死因子-α(TNF-α))或通过PMN与DC的细胞接触,诱导DC表面标志物CD40、CD80、主要组织相容性复合体II类分子(Iab)和CD86的强烈上调。LPS-PMN还刺激DC产生白细胞介素-12(IL-12)和TNF-α。此外,由LPS-PMN激活的纯化DC能够向T细胞呈递特异性抗原,并通过产生大量干扰素-γ(IFN-γ)但少量白细胞介素-4(IL-4)来驱动Th1分化。我们的结果表明PMN在适应性免疫反应中对DC功能具有调节作用,从而在固有免疫和适应性免疫之间建立了联系。