Fedele Giorgio, Celestino Ignacio, Spensieri Fabiana, Frasca Loredana, Nasso Maria, Watanabe Mineo, Remoli Maria Elena, Coccia Eliana Marina, Altieri Fabio, Ausiello Clara Maria
Department of Infectious, Parasitic and Immune-mediated Diseases, Anti-infectious Immunity Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Microbes Infect. 2007 Jun;9(7):855-63. doi: 10.1016/j.micinf.2007.03.002. Epub 2007 Mar 12.
Bordetella pertussis has a distinctive cell wall lipooligosaccharide (LOS) that is released from the bacterium during bacterial division and killing. LOS directly participates in host-bacterial interactions, in particular influencing the dendritic cells' (DC) immune regulatory ability. We analyze LOS mediated toll-like receptor (TLR) activation and dissect the role played by LOS on human monocyte-derived (MD)DC functions and polarization of the host T cell response. LOS activates TLR4-dependent signaling and induces mature MDDC able to secrete IL-10. LOS-matured MDDC enhance allogeneic presentation and skew T helper (Th) cell polarization towards a Th2 phenotype. LOS protects MDDC from undergoing apoptosis, prolonging their longevity and their functions. Compared to Escherichia coli lipopolysaccharide (LPS), the classical DC maturation stimulus, LOS was a less efficient inducer of TLR4 signaling, MDDC maturation, IL-10 secretion and allogeneic T cell proliferation and it was not able to induce IL-12p70 production in MDDC. However, the MDDC apoptosis protection exerted by LOS and LPS were comparable. In conclusion, LOS treated MDDC are able to perform antigen presentation in a context that promotes licensing of Th2 effectors. Considering these properties, the use of LOS in the formulation of acellular pertussis vaccines to potentiate protective and adjuvant capacity should be taken into consideration.
百日咳博德特氏菌具有独特的细胞壁脂寡糖(LOS),在细菌分裂和死亡过程中从细菌中释放出来。LOS直接参与宿主与细菌的相互作用,特别是影响树突状细胞(DC)的免疫调节能力。我们分析了LOS介导的Toll样受体(TLR)激活,并剖析了LOS在人单核细胞衍生的(MD)DC功能以及宿主T细胞反应极化中所起的作用。LOS激活依赖TLR4的信号传导,并诱导能够分泌IL-10的成熟MDDC。LOS成熟的MDDC增强同种异体呈递,并使T辅助(Th)细胞极化偏向Th2表型。LOS保护MDDC免于凋亡,延长其寿命及其功能。与经典的DC成熟刺激物大肠杆菌脂多糖(LPS)相比,LOS是TLR4信号传导、MDDC成熟、IL-10分泌和同种异体T细胞增殖的低效诱导剂,并且它不能诱导MDDC产生IL-12p70。然而,LOS和LPS对MDDC凋亡的保护作用相当。总之,LOS处理的MDDC能够在促进Th2效应器许可的背景下进行抗原呈递。考虑到这些特性,应考虑在无细胞百日咳疫苗配方中使用LOS来增强保护和佐剂能力。