DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination biases towards T helper 1 responses and enhances protection against Leishmania major infection in mice

DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination biases towards T helper 1 responses and enhances protection against Leishmania major infection in mice
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DOI:
10.1128/iai.72.8.4924-4928.2004
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发表时间:
2004-08-01
影响因子:
3.1
通讯作者:
Stober, CB
Stober, CB
中科院分区:
医学2区
文献类型:
--
作者:
Lange, UG;Mastroeni, P;Stober, CB

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细胞内病原体感染的成功解决需要γ干扰素(ifn - γ)。DNA疫苗通过toll样受体9 (TLR9)触发树突状细胞(DC)释放白细胞介素-12 (IL-12),从而促进T辅助细胞1 (Th1)应答。在人类中,TLR9仅限于浆细胞样DC。本研究表明,与单独接种DNA疫苗相比,DNA-肠沙门氏菌血清鼠伤寒菌引物-加强疫苗接种,提供了在髓系DC上结合TLR4的替代配体,强烈倾向于Th1应答。这导致免疫球蛋白G2a (IgG2a)应答比IgG1应答更高,ifn - γ应答比IL-10 CD4(+)- t细胞应答更高,并且在易感BALB/c小鼠中增强了对利什曼原虫主要感染的保护。
Successful resolution of infections by intracellular pathogens requires gamma interferon (IFN-gamma). DNA vaccines promote T helper 1 (Th1) responses by triggering interleukin-12 (IL-12) release by dendritic cells (DC) through Toll-like receptor 9 (TLR9). In humans TLR9 is restricted to plasmacytoid DC. Here we show that DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination, which provides alternative ligands to bind TLR4 on myeloid DC, strongly biases towards Th1 responses compared to vaccination with DNA alone. This results in higher immunoglobulin G2a (IgG2a) responses compared to IgG1 responses, higher IFN-gamma responses compared to IL-10 CD4(+)-T-cell responses, and enhanced protection against Leishmania major infection in susceptible BALB/c mice.