Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen.
Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen.
复制标题
曼氏血吸虫感染会改变 Th1/Th2 细胞因子对非寄生虫抗原的反应。
DOI：
--
复制
发表时间：
1992
影响因子：
4.4
通讯作者：
J. A. Berzofsky
中科院分区：
文献类型：
--
作者：
M. Kullberg;Edward J. Pearce;S. Hieny;Alan Sher;J. A. Berzofsky
研究表明，小鼠感染曼氏血吸虫后，寄生虫银和丝裂原诱导的Th1细胞因子（IL-2和ifn - γ）分泌下调，同时Th2细胞因子（IL-4、IL-5和IL-10）分泌增加，提示淋巴细胞功能普遍失衡。在本研究中，我们研究了曼氏梭菌感染是否也会影响对非寄生虫Ag -抹香鲸肌红蛋白（SwMb）的免疫反应特征。当用SwMb刺激血吸虫感染的免疫动物的脾脏细胞（SC）时，发现它们每CD4+细胞产生的IL-2和ifn - γ比免疫未感染动物的应答显著降低（分别降低45%和59%）。此外，swmb诱导的每CD4+细胞分泌的IL-4在感染小鼠的SC培养中增加了三倍。在相同的培养中未检测到肌红蛋白诱导的IL-5。除了SC培养外，IL-10特异性中和mAb部分恢复了感染小鼠对SwMb的抑制ifn - γ反应，这表明IL-10在观察到的下调中起作用。mansoni感染小鼠也表现出对SwMb的抗体反应受损，其水平为未感染小鼠的10%至27%，尽管IgG同型无明显差异。综上所述，这些结果表明，mansoni感染诱导了对不相关的外来免疫原和寄生虫Ag本身的Th1反应的下调和Th2反应的升高。这些发现的一个含义是，蠕虫感染的个体可能改变了细胞介导的免疫功能，以对抗其他微生物。
Schistosoma mansoni infection in the mouse has been shown to be accompanied by a down-regulation in parasite-Ag- and mitogen-induced Th1 cytokine secretion (IL-2 and IFN-gamma) with a simultaneous increase in the production of Th2 cytokines (IL-4, IL-5, and IL-10), suggesting a generalized imbalance in lymphocyte function. In the present study, we examined whether infection with S. mansoni would also influence the character of immune responses to a non-parasite Ag, sperm whale myoglobin (SwMb). When spleen cells (SC) from schistosome-infected SwMb-immunized animals were stimulated with SwMb, their production of IL-2 and IFN-gamma per CD4+ cell was found to be significantly reduced (by 45% and 59%, respectively) compared with the responses observed in immunized uninfected animals. Moreover, SwMb-induced secretion of IL-4 per CD4+ cell was increased threefold in SC cultures from infected mice. No myoglobin-induced IL-5 was detected in the same cultures. Addition to SC cultures of a neutralizing mAb specific for IL-10 partly restored the suppressed IFN-gamma response to SwMb seen in infected mice, suggesting a role for IL-10 in the observed down-regulation. S. mansoni-infected mice also showed an impaired antibody response to SwMb, with levels ranging from 10% to 27% of those observed in uninfected mice, although no differences in IgG isotype were evident. Taken together, these results suggest that infection with S. mansoni induces a down-regulation of Th1 responses and elevation of Th2 responses to unrelated foreign immunogens as well as to parasite Ag themselves. One implication of these findings is that helminth-infected individuals may have altered cell-mediated immune function to other microbial agents.