Boppana V D, Thangamani S, Adler A J, Wikel S K
Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA.
Parasite Immunol. 2009 Jun;31(6):287-95. doi: 10.1111/j.1365-3024.2009.01096.x.
Mosquitoes represent the most important vector for transmitting pathogens that cause human disease. Central to pathogen transmission is the ability to divert the host immune system away from Th1 and towards Th2 responsiveness. Identification of the mosquito factor(s) critical for programming Th2 responsiveness should therefore lead to strategies to neutralize their function and thus prevent disease transmission. In the current study, we used a TCR transgenic adoptive transfer system to screen gene products present in the saliva of the mosquito Aedes aegypti for their ability to programme CD4 T cells to express the signature Th2 cytokine IL-4. The clone SAAG-4 encodes a secreted protein with a predicted size of 20 kDa whose function has previously been uncharacterized. Notably, SAAG-4 reduced host CD4 T cell expression of the signature Th1 cytokine IFN-gamma while simultaneously increasing expression of IL-4. SAAG-4 is therefore the first identified mosquito factor that can programme Th2 effector CD4 T cell differentiation.
蚊子是传播导致人类疾病的病原体的最重要媒介。病原体传播的关键在于能够使宿主免疫系统从Th1反应转向Th2反应。因此,鉴定对编程Th2反应至关重要的蚊子因子,应能产生中和其功能从而预防疾病传播的策略。在当前研究中,我们使用TCR转基因过继转移系统,筛选埃及伊蚊唾液中存在的基因产物,以检测其编程CD4 T细胞表达标志性Th2细胞因子IL-4的能力。克隆SAAG-4编码一种预测大小为20 kDa的分泌蛋白,其功能此前未被表征。值得注意的是,SAAG-4降低了宿主CD4 T细胞标志性Th1细胞因子IFN-γ的表达,同时增加了IL-4的表达。因此,SAAG-4是首个被鉴定出的能够编程Th2效应性CD4 T细胞分化的蚊子因子。