Objective：In this review,to illustrate the resistance mechanism for pathogen insult,we discussed the role of the intestinal microbiome in promoting resistance to local gastrointestinal tract infections and to respira...Objective：In this review,to illustrate the resistance mechanism for pathogen insult,we discussed the role of the intestinal microbiome in promoting resistance to local gastrointestinal tract infections and to respiratory tract infections.Data Sources：The review was based on data obtained from the published research articles.Study Selection：A total of 49 original articles were selected in accordance with our main objective to illustrate the resistance mechanism（s） by which commensal microbiota can contribute to host defense against local and systemic infections.Results：Diverse microorganisms colonize human environmentally exposed surfaces such as skin,respiratory tract,and gastrointestinal tract.Co-evolution has resulted in these microbes with extensive and diverse impacts on multiple aspects of host biological functions.During the last decade,high-throughput sequencing technology developed has been applied to study commensal microbiota and their impact on host biological functions.By using pathogen recognition receptors pathway and nucleotide binding oligomerization domain-like receptors pathway,the commensal microbiome promotes resistance to local and systemic infections,respectively.To protect against the local infections,the microbiome functions contain the following：the competing for sites of colonization,direct production of inhibition molecules or depletion of nutrients needed for pathogens,and priming immune defenses against pathogen insult.At the same time,with the purpose to maintain homeostasis,the commensal bacteria can program systemic signals toward not only local tissue but also distal tissue to modify their function for infections accordingly.Conclusions：Commensal bacteria play an essential role in protecting against infections,shaping and regulating immune responses,and maintaining host immune homeostasis.展开更多
炎症在众多疾病的发展中起着重要作用,而核苷酸结合寡聚化域样受体蛋白3(nucleotide binding oligomerization domain like receptors protein 3,NLRP3)信号通路是其中关键的一环。NLRP3可通过自组装后形成炎性小体激活半胱氨酸天冬氨...炎症在众多疾病的发展中起着重要作用,而核苷酸结合寡聚化域样受体蛋白3(nucleotide binding oligomerization domain like receptors protein 3,NLRP3)信号通路是其中关键的一环。NLRP3可通过自组装后形成炎性小体激活半胱氨酸天冬氨酸蛋白水解酶-1,进而激活IL-1β和IL-18前体引发炎症;而马来酸胺乙基青蒿素、骨化三醇、非诺贝特、MCC950、白藜芦醇等药物则可通过抑制NLRP3信号通路的不同位点(如促进核转录因子κB、半胱氨酸天冬氨酸蛋白水解酶-1、NLRP3等)的表达以降低IL-18和IL-1β的表达,进而实现控制氧化应激和慢性炎症进展,最终实现治疗干眼、糖尿病视网膜病变和AMD等眼病的目的。目前NLRP3信号通路抑制剂治疗眼病的相关研究尚停留在较为早期的动物模型及体外实验,其于眼科疾病的应用研究有待进一步拓展。展开更多
基金Beijing Natural Science Foundation （7142021）, Capital Medical University Basic-Clinical Medical Research Funding （15JL 13）, Capital Medical University Young Teachers Research Funding （2014PY45）.
文摘Objective：In this review,to illustrate the resistance mechanism for pathogen insult,we discussed the role of the intestinal microbiome in promoting resistance to local gastrointestinal tract infections and to respiratory tract infections.Data Sources：The review was based on data obtained from the published research articles.Study Selection：A total of 49 original articles were selected in accordance with our main objective to illustrate the resistance mechanism（s） by which commensal microbiota can contribute to host defense against local and systemic infections.Results：Diverse microorganisms colonize human environmentally exposed surfaces such as skin,respiratory tract,and gastrointestinal tract.Co-evolution has resulted in these microbes with extensive and diverse impacts on multiple aspects of host biological functions.During the last decade,high-throughput sequencing technology developed has been applied to study commensal microbiota and their impact on host biological functions.By using pathogen recognition receptors pathway and nucleotide binding oligomerization domain-like receptors pathway,the commensal microbiome promotes resistance to local and systemic infections,respectively.To protect against the local infections,the microbiome functions contain the following：the competing for sites of colonization,direct production of inhibition molecules or depletion of nutrients needed for pathogens,and priming immune defenses against pathogen insult.At the same time,with the purpose to maintain homeostasis,the commensal bacteria can program systemic signals toward not only local tissue but also distal tissue to modify their function for infections accordingly.Conclusions：Commensal bacteria play an essential role in protecting against infections,shaping and regulating immune responses,and maintaining host immune homeostasis.
文摘炎症在众多疾病的发展中起着重要作用,而核苷酸结合寡聚化域样受体蛋白3(nucleotide binding oligomerization domain like receptors protein 3,NLRP3)信号通路是其中关键的一环。NLRP3可通过自组装后形成炎性小体激活半胱氨酸天冬氨酸蛋白水解酶-1,进而激活IL-1β和IL-18前体引发炎症;而马来酸胺乙基青蒿素、骨化三醇、非诺贝特、MCC950、白藜芦醇等药物则可通过抑制NLRP3信号通路的不同位点(如促进核转录因子κB、半胱氨酸天冬氨酸蛋白水解酶-1、NLRP3等)的表达以降低IL-18和IL-1β的表达,进而实现控制氧化应激和慢性炎症进展,最终实现治疗干眼、糖尿病视网膜病变和AMD等眼病的目的。目前NLRP3信号通路抑制剂治疗眼病的相关研究尚停留在较为早期的动物模型及体外实验,其于眼科疾病的应用研究有待进一步拓展。
