Toll样受体家族(Toll like receptors,TLRs)是先天性免疫系统进化过程中形成的非常保守的模式识别受体家族,Toll样受体2(Toll-like receptors 2,TLR2)是已经克隆的Toll样受体家族中表达范围最广,识别病原微生物种类最多的成员。它可单...Toll样受体家族(Toll like receptors,TLRs)是先天性免疫系统进化过程中形成的非常保守的模式识别受体家族,Toll样受体2(Toll-like receptors 2,TLR2)是已经克隆的Toll样受体家族中表达范围最广,识别病原微生物种类最多的成员。它可单独或协同其他Toll样受体家族成员完成对病原体相关分子模式的识别,触发机体对致病微生物的级联免疫应答,尤其是针对细胞毒素的抗炎症反应具有重要的作用,已经成为多种疾病治疗的新靶点。文章对哺乳动物TLR2的分布,结构特征,配体识别,信号转导及其生物学功能的最新研究进展进行了综述。展开更多
Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the vi...Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is res-ponsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.展开更多
AIM: To investigate roles of surfactant protein D (SP-D) and relative cytokines in human corneal epithelial (HCE) cells Exposed to aspergillus fumigatus (AF) antigens. METHODS: HCE cells cultured 47 in vitro with AF a...AIM: To investigate roles of surfactant protein D (SP-D) and relative cytokines in human corneal epithelial (HCE) cells Exposed to aspergillus fumigatus (AF) antigens. METHODS: HCE cells cultured 47 in vitro with AF antigens and sampled at 0, 0.5, 1 hour, 2, 4, 6 and 8 hours. The Expression of SP-D mRNA was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).The expression of SP-D protein was shown by ELISA and immunocytochemistry SP methods. The expression of NF-kappa B and relative downstream cytokines such as TNF-alpha, IL-1 beta, IL-8 and IL-10 in supernatant fluid were measured by ELISA. RESULTS: SP-D mRNA and protein were detected in untreated HCE cells. The expression of SP-D and the relative downstream cytokines rose after being stimulated with AF antigens. SP-D mRNA began to rise at 0.5 hour and the most significantly peak was in 2 hours. The protein of SP-D in supernatant fluid had the same trend with mRNA. Immunocytochemistry of SP-D showed positive expression and gradually increased to 6 hours, and then the expression began to decline. NF-kappa B was activated after treated by AF antigens and the changes had correlation with SP-D. TNF-alpha, IL-1 beta, IL-8 and IL-10 began to rise after given AF antigens 1 hour and were 1.82, 1.43, 1.12 and 1.28 times higher than the untreated HCE cells separately. The expression of TNF-alpha and IL-1 beta reached the peak at 2 hours, separately 2.80 and 2.86 times than the untreated. The expression of IL-8 and IL-10 gradually increased with a time-dependent manner. ' CONCLUSION: HCE cells exists SP-D and it may play a significant role in pathogenesis of keratomycosis. AF may induce human corneal epithelial cells to express inflammatory cytokines via SP-D and NF-kappa B pathway. SP-D possibly mediates the recognition to AF mycelium.展开更多
STING(stimulator of interferon genes)是天然免疫信号通路中一种新发现的蛋白质,在防御病毒及胞内细菌感染、介导Ⅰ型IFN产生过程中发挥重要功能.来自病原体的B型DNA与5′-3p dsRNA暴露在宿主细胞中后被相应的模式识别受体识别,通过...STING(stimulator of interferon genes)是天然免疫信号通路中一种新发现的蛋白质,在防御病毒及胞内细菌感染、介导Ⅰ型IFN产生过程中发挥重要功能.来自病原体的B型DNA与5′-3p dsRNA暴露在宿主细胞中后被相应的模式识别受体识别,通过不同的通路传递信号给STING.STING随后通过相似的机制招募TBK1激活IRF3,诱导干扰素表达.对细菌中的环二核苷酸c-di-GMP和c-di-AMP,STING则可以直接作为模式识别受体引发Ⅰ型干扰素反应.此外STING还能激活STAT6诱导特异趋化因子产生,吸引各种免疫细胞抵抗病毒感染.本文通过对STING的发现、结构、定位、功能、机理以及调节机制进行综述,以期为揭示病毒逃逸天然免疫调节机制和抗病毒新型免疫调节剂提供新的思路.展开更多
文摘Toll样受体家族(Toll like receptors,TLRs)是先天性免疫系统进化过程中形成的非常保守的模式识别受体家族,Toll样受体2(Toll-like receptors 2,TLR2)是已经克隆的Toll样受体家族中表达范围最广,识别病原微生物种类最多的成员。它可单独或协同其他Toll样受体家族成员完成对病原体相关分子模式的识别,触发机体对致病微生物的级联免疫应答,尤其是针对细胞毒素的抗炎症反应具有重要的作用,已经成为多种疾病治疗的新靶点。文章对哺乳动物TLR2的分布,结构特征,配体识别,信号转导及其生物学功能的最新研究进展进行了综述。
基金Supported by Grants of Yantai Science and Technology Plan Project,No.2012116
文摘Hepatitis B virus(HBV) infection is a major public healthproblem worldwide. HBV is not directly cytotoxic to infected hepatocytes; the clinical outcome of infection results from complicated interactions between the virus and the host immune system. In acute HBV infection, initiation of a broad, vigorous immune response is res-ponsible for viral clearance and self-limited inflammatory liver disease. Effective and coordinated innate and adaptive immune responses are critical for viral clearance and the development of long-lasting immunity. Chronic hepatitis B patients fail to mount efficient innate and adaptive immune responses to the virus. In particular, HBV-specific cytotoxic T cells, which are crucial for HBV clearance, are hyporesponsiveness to HBV infection. Accumulating experimental evidence obtained from the development of animal and cell line models has highlighted the importance of innate immunity in the early control of HBV spread. The virus has evolved immune escape strategies, with higher HBV loads and HBV protein concentrations associated with increasing impairment of immune function. Therefore, treatment of HBV infection requires inhibition of HBV replication and protein expression to restore the suppressed host immunity. Complicated interactions exist not only between innate and adaptive responses, but also among innate immune cells and different components of adaptive responses. Improved insight into these complex interactions are important in designing new therapeutic strategies for the treatment HBV infection. In this review, we summarize the current knowledge regarding the cross-talk between the innate and adaptive immune responses and among different immunocytes in HBV infection.
基金National Natural Science Foundation of China(No.81170825)
文摘AIM: To investigate roles of surfactant protein D (SP-D) and relative cytokines in human corneal epithelial (HCE) cells Exposed to aspergillus fumigatus (AF) antigens. METHODS: HCE cells cultured 47 in vitro with AF antigens and sampled at 0, 0.5, 1 hour, 2, 4, 6 and 8 hours. The Expression of SP-D mRNA was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).The expression of SP-D protein was shown by ELISA and immunocytochemistry SP methods. The expression of NF-kappa B and relative downstream cytokines such as TNF-alpha, IL-1 beta, IL-8 and IL-10 in supernatant fluid were measured by ELISA. RESULTS: SP-D mRNA and protein were detected in untreated HCE cells. The expression of SP-D and the relative downstream cytokines rose after being stimulated with AF antigens. SP-D mRNA began to rise at 0.5 hour and the most significantly peak was in 2 hours. The protein of SP-D in supernatant fluid had the same trend with mRNA. Immunocytochemistry of SP-D showed positive expression and gradually increased to 6 hours, and then the expression began to decline. NF-kappa B was activated after treated by AF antigens and the changes had correlation with SP-D. TNF-alpha, IL-1 beta, IL-8 and IL-10 began to rise after given AF antigens 1 hour and were 1.82, 1.43, 1.12 and 1.28 times higher than the untreated HCE cells separately. The expression of TNF-alpha and IL-1 beta reached the peak at 2 hours, separately 2.80 and 2.86 times than the untreated. The expression of IL-8 and IL-10 gradually increased with a time-dependent manner. ' CONCLUSION: HCE cells exists SP-D and it may play a significant role in pathogenesis of keratomycosis. AF may induce human corneal epithelial cells to express inflammatory cytokines via SP-D and NF-kappa B pathway. SP-D possibly mediates the recognition to AF mycelium.
文摘天然免疫系统是动物抵御病原入侵的第一道防线,在机体抗病毒感染过程中发挥重要作用,模式识别受体(pattern-recognition receptors,PRRs)是天然免疫系统的重要成分,动物机体的抗病毒免疫机制是由一系列PRRs对病原体的识别所启动的。近年来识别和感受病原体的一系列动物PRRs受到广泛关注,成为动物医学领域的研究热点,为揭示动物复杂的抗病毒天然免疫反应提供了新思路。该文简要介绍动物Toll样受体(Toll-like receptors,TLRs)和维甲酸诱导基因Ⅰ样受体(RIG-I like receptors,RLRs)的分子特征及其介导的抗病毒天然免疫作用研究进展。
文摘STING(stimulator of interferon genes)是天然免疫信号通路中一种新发现的蛋白质,在防御病毒及胞内细菌感染、介导Ⅰ型IFN产生过程中发挥重要功能.来自病原体的B型DNA与5′-3p dsRNA暴露在宿主细胞中后被相应的模式识别受体识别,通过不同的通路传递信号给STING.STING随后通过相似的机制招募TBK1激活IRF3,诱导干扰素表达.对细菌中的环二核苷酸c-di-GMP和c-di-AMP,STING则可以直接作为模式识别受体引发Ⅰ型干扰素反应.此外STING还能激活STAT6诱导特异趋化因子产生,吸引各种免疫细胞抵抗病毒感染.本文通过对STING的发现、结构、定位、功能、机理以及调节机制进行综述,以期为揭示病毒逃逸天然免疫调节机制和抗病毒新型免疫调节剂提供新的思路.
文摘随着社会经济的快速发展及生活习惯的改变,肥胖、2型糖尿病和非酒精性脂肪性肝病(nonalcoholic fatty liver diseases,NAFLD)在国内流行。流行病学调查表明,中国成人不同程度肥胖、2型糖尿病及脂肪肝者占15%或更高。NAFLD是一类脂肪性肝脏疾病的总称,与饮酒无关,其共性是甘油三酯在肝实质细胞的大量堆积。10%～20%NAFLD患者可能进展为非酒精性脂肪性肝炎(nonalcoholicsteatohepatitis,NASH),后者中约20%可能进一步进展为肝硬化甚至肝细胞癌。Day等于1998年提出了"二次打击学说"来解释脂肪性肝炎的形成。大量调查显示,维生素D缺乏与脂肪肝和代谢综合征的发生密切相关,但作用机制尚未明确。维生素D受体(vitamin D receptor,VDR)在回肠帕内特细胞(Paneth cells)中大量表达,提示维生素D信号在小肠的先天性免疫及平衡肠道菌群方面发挥关键作用。近年来,动物模型研究发现充足的维生素D可促进帕内特细胞外分泌抗菌肽(alpha-defensins),平衡肠道菌群,减少内毒素入血,从而预防脂肪肝的形成。此外,有研究表明维生素D信号能够诱导调节性T细胞(regulatory T cells,Tregs),抑制Th1及Th17应答,维持机体免疫平衡。因此,开展大规模临床试验来验证维生素D对NAFLD的疗效及分子机制十分必要。
