LT-IIc, a new member of the type II heat-labile enterotoxin family, exhibits potent immunomodulatory properties that are different from those induced by LT-IIa or LT-IIb.
LT-IIc, a new member of the type II heat-labile enterotoxin family, exhibits potent immunomodulatory properties that are different from those induced by LT-IIa or LT-IIb.
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DOI：
10.1016/j.vaccine.2010.11.020
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发表时间：
2011-01-17
期刊：
影响因子：
5.5
通讯作者：
Connell, Terry D.
中科院分区：
文献类型：
--
作者：
Nawar, Hesham F.;Greene, Christopher J.;Lee, Chang Hoon;Mandell, Lorrie M.;Hajishengallis, George;Connell, Terry D.
大量的人类病原体侵入和/或定植在粘膜表面。然而，通过粘膜疫苗接种对这些病原体产生强烈的保护性免疫反应，受到粘膜内源性调节系统的阻碍，该系统会抑制对外来抗原（Ag）的反应。为了克服这些天然屏障，必须使用粘膜佐剂。利用小鼠粘膜免疫模型和变形链球菌的弱免疫原AgI/II，发现热不稳定肠毒素家族II型亚群的新成员LT-IIc具有强效的粘膜佐剂特性。与仅用AgI/II鼻内免疫的小鼠相比，AgI/II与LT-IIc共同给药增强了唾液和阴道液中ag特异性IgA抗体的产生以及血清中ag特异性IgA和IgG的产生。IL-2、IL-6、IL-17、IFN-γ和TNF-α的分泌在AgI/ ii刺激的小鼠脾细胞中得到增强，这些细胞接受了LT-IIc作为粘膜佐剂。相反，IL-10的分泌在这些细胞中被抑制。这种细胞因子分泌模式表明，LT-IIc刺激Th1和Th2免疫反应。与II型亚群的原始成员LT-IIa和LT-IIb相反，LT-IIc显著增强了与LPS共培养的腹腔巨噬细胞中IL-1α和IL-1β的分泌。此外，LT-IIc的B五聚体亚基增加了骨髓源树突状细胞对银的摄取，其水平超过了使用LPS或LT-IIa或LT-IIb的B五聚体所达到的水平。这些数据证实，LT-IIc是一种强粘膜佐剂，具有与LT-IIa和LT-IIb不同的免疫调节特性，并且具有可用于疫苗开发的免疫调节特性。
A plethora of human pathogens invade and/or colonize mucosal surfaces. Elaboration of strong, protective immune responses against those pathogens by mucosal vaccination, however, is hampered by endogenous regulatory systems in the mucosae that dampen responses to foreign antigens (Ag). To overcome those natural barriers, mucosal adjuvants must be employed. Using a mouse mucosal immunization model and AgI/II, a weak immunogen from Streptococcus mutans, LT-IIc, a new member of the type II subgroup of the heat-labile enterotoxin family, was shown to have potent mucosal adjuvant properties. In comparison to mice intranasally immunized only with AgI/II, co-administration of AgI/II with LT-IIc enhanced production of Ag-specific IgA antibodies in the saliva and vaginal fluids and Ag-specific IgA and IgG in the serum. Secretion of IL-2, IL-6, IL-17, IFN-γ, and TNF-α was enhanced in cultures of AgI/II-stimulated splenic cells isolated from mice that had received LT-IIc as a mucosal adjuvant. In contrast, secretion of IL-10 was suppressed in those cells. This pattern of cytokine secretion suggested that LT-IIc stimulates both Th1 and Th2 immune responses. In contrast to LT-IIa and LT-IIb, the original members of the type II subgroup that also are mucosal adjuvants, LT-IIc dramatically enhanced secretion of IL-1α and IL-1β in peritoneal macrophages that had been co-cultured with LPS. Furthermore, the B pentameric subunit of LT-IIc augmented uptake of Ag by bone marrow-derived dendritic cells to levels that exceeded those attained by use of LPS or by the B pentamers of LT-IIa or LT-IIb. These data confirmed that LT-IIc is a strong mucosal adjuvant with immunomodulatory properties that are distinguishable from those of LT-IIa and LT-IIb and which has immunomodulatory properties that may be exploitable in vaccine development.
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DOI：
10.4049/jimmunol.0803737
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Liang S;Hosur KB;Lu S;Nawar HF;Weber BR;Tapping RI;Connell TD;Hajishengallis G
通讯作者：
Hajishengallis G
影响因子：
3.1
作者：
CONNELL, TD;HOLMES, RK
通讯作者：
HOLMES, RK
影响因子：
3.1
作者：
Nawar, Hesham F.;King-Lyons, Natalie D.;Connell, Terry D.
通讯作者：
Connell, Terry D.
影响因子：
3.3
作者：
Nardi, ARM;Salvadori, MR;Yano, T
通讯作者：
Yano, T
影响因子：
3.1
作者：
FUKUTA, S;MAGNANI, JL;GINSBURG, V
通讯作者：
GINSBURG, V