Vaccination routes that fail to elicit protective immunity against Schistosoma mansoni induce the production of TGF-beta, which down-regulates macrophage antiparasitic activity.
Vaccination routes that fail to elicit protective immunity against Schistosoma mansoni induce the production of TGF-beta, which down-regulates macrophage antiparasitic activity.
复制标题
未能引发针对曼氏血吸虫的保护性免疫的疫苗接种途径会诱导TGF-β的产生，从而下调巨噬细胞的抗寄生虫活性。
作者：
M. Williams;P. Caspar;I. Oswald;H. K. Sharma;O. Pankewycz;A. Sher;S. James
C57BL/6小鼠皮内免疫(I.D.)使用卡介苗(BCG)加灭活皮肤期血吸虫幼虫可预防后续感染曼氏血吸虫，而静脉注射免疫。或者I.M.路线不是保护性的。此外，以前通过非保护性静脉注射接种的疫苗。路线干扰了随后通过身份识别诱导保护的能力。疫苗接种，这表明调用了抑制性反应。有证据表明活化的巨噬细胞(M Phi)在血吸虫病免疫中起效应细胞的作用，我们研究了保护性和非保护性免疫小鼠的脾细胞产生M Phi激活和失活细胞因子的能力。暴露于Ag的上清液(SNS)可刺激I.D.的脾细胞，但不能静脉注射。或肌肉注射，免疫的小鼠通过依赖干扰素-γ和肿瘤坏死因子-α的机制，激活炎性M-Phi，在体外杀死血吸虫幼虫。未观察到M.Phi在I.D.中优先诱导激活Th1细胞因子干扰素-γ和IL-2的证据。来自非保护性动物的脾细胞也不会产生更高水平的Th2相关细胞因子IL-4和IL-10，这两种细胞因子被认为可以防止M Phi激活。然而，在未受保护的小鼠的SNS中检测到了转化生长因子-β。此外，在这些SNS中检测到的M-Phi抑制活性是热稳定的，并被抗转化生长因子-β抗体中和，这表明转化生长因子-β的产生至少是免疫失败的部分原因。和静脉注射。免疫小鼠以产生对曼氏血吸虫的免疫力。因此，诱导下调的细胞因子可能是限制某些疫苗接种方案有效性的一个重要因素。
C57BL/6 mice immunized intradermally (i.d.) with bacillus Calmette Guerin (BCG) plus killed skin-stage schistosomula are protected against subsequent infection with Schistosoma mansoni, whereas immunization by i.v. or i.m. routes is not protective. Moreover, previous immunization via the nonprotective i.v. route interfered with the ability to subsequently induce protection by i.d. vaccination, suggesting that inhibitory responses are invoked. Given the evidence that activated macrophages (M phi) play a role as effector cells in protection against schistosomiasis, we investigated the ability of spleen cells from protected and nonprotected immunized mice to produce M phi activating and deactivating cytokines. Exposure to supernatant fluids (SNs) from Ag stimulated spleen cells of i.d., but not i.v. or i.m., immunized mice activated inflammatory M phi for in vitro killing of schistosome larvae, through a mechanism dependent on both IFN gamma and TNF-alpha. No evidence was observed for the preferential induction of the M phi activating Th1 cytokines IFN-gamma and IL-2 in i.d. immunized mice, nor did spleen cells from nonprotected animals produce higher levels of the Th2 associated cytokines IL-4 and IL-10, which are known to prevent M phi activation. TGF-beta was, however, detected in SNs from unprotected mice. Moreover, the M phi inhibitory activity detected in these SNs was heat stable and neutralized by anti-TGF-beta Abs, suggesting that production of TGF-beta is at least partially responsible for the failure of i.m. and i.v. immunized mice to develop immunity to S. mansoni. Thus, the induction of down-regulatory cytokines may be an important factor limiting the efficacy of certain vaccination protocols.