The human gastrointestinal （GI） tract is colonized by non-pathogenic commensal microflora and frequently exposed to many pathogenic organisms. For the maintenance of GI homeostasis, the host must discriminate betwee...The human gastrointestinal （GI） tract is colonized by non-pathogenic commensal microflora and frequently exposed to many pathogenic organisms. For the maintenance of GI homeostasis, the host must discriminate between pathogenic and non-pathogenic organisms and initiate effective and appropriate immune and inflammatory responses. Mammalian tolllike receptors （TLRs） are members of the patternrecognition receptor （PRR） family that plays a central role in the initiation of innate cellular immune responses and the subsequent adaptive immune responses to microbial pathogens. Recent studies have shown that gastrointestinal epithelial cells express almost all TLR subtypes characterized to date and that the expression and activation of TLRs in the GI tract are tightly and coordinately regulated. This review summarizes the current understanding of the crucial dual roles of TLRs in the development of host innate and adaptive immune responses to GI infections and the maintenance of the immune tolerance to commensal bacteria through downregulation of surface expression of TLRs in intestinal epithelial cells.展开更多
Noroviruses(NoVs) are the main cause of viral gastroenteritis outbreaks worldwide, and oysters are the most common carriers of NoV contamination and transmission. NoVs bind specifically to oyster tissues through histo...Noroviruses(NoVs) are the main cause of viral gastroenteritis outbreaks worldwide, and oysters are the most common carriers of NoV contamination and transmission. NoVs bind specifically to oyster tissues through histo-blood group antigens(HBGAs), and this facilitates virus accumulation and increases virus persistence in oysters. To investigate the interaction of HBGAs in Pacific oysters with GⅡ.4 NoV, we examined HBGAs with ELISAs and investigated binding patterns with oligosaccharide-binding assays using P particles as a model of five GⅡ.4 NoV capsids. The HBGAs in the gut and gills exhibited polymorphisms. In the gut, type A was detected(100%), whereas type Leb(91.67%) and type A(61.11%) were both observed in the gills. Moreover, we found that seasonal NoV gastroenteritis outbreaks were not significantly associated with the specific HBGAs detected in the oyster gut and gills. In the gut, we found that strain-2006 b and strain-96/96 US bound to type A and H1 but only weakly bound to type Leb; in contrast, the Camberwell and Hunter strains exhibited weak binding to types H1 and Ley, and strain-Sakai exhibited no binding to any HBGA type. In the gills, strain-96/96 US and strain-2006 b bound to type Leb but only weakly bound to type H1; strains Camberwell, Hunter, and Sakai did not bind to oyster HBGAs. Assays for oligosaccharide binding to GⅡ.4 NoV P particles showed that strain-95/96 US and strain-2006 b strongly bound to type A, B, H1, Leb, and Ley oligosaccharides, while strains Camberwell and Hunter showed weak binding ability to type H1 and Ley oligosaccharides and strain-Sakai showed weak binding ability to type Leb and Ley oligosaccharides. Our study presents new information and enhances understanding about the mechanism for NoV accumulation in oysters. Further studies of multiple NoV-tissue interactions might assist in identifying new or improved strategies for minimizing contamination, including HBGA-based attachment inhibition or depuration.展开更多
基金Supported by the National Research Council Canada and the National Institutes of Health, United States
文摘The human gastrointestinal （GI） tract is colonized by non-pathogenic commensal microflora and frequently exposed to many pathogenic organisms. For the maintenance of GI homeostasis, the host must discriminate between pathogenic and non-pathogenic organisms and initiate effective and appropriate immune and inflammatory responses. Mammalian tolllike receptors （TLRs） are members of the patternrecognition receptor （PRR） family that plays a central role in the initiation of innate cellular immune responses and the subsequent adaptive immune responses to microbial pathogens. Recent studies have shown that gastrointestinal epithelial cells express almost all TLR subtypes characterized to date and that the expression and activation of TLRs in the GI tract are tightly and coordinately regulated. This review summarizes the current understanding of the crucial dual roles of TLRs in the development of host innate and adaptive immune responses to GI infections and the maintenance of the immune tolerance to commensal bacteria through downregulation of surface expression of TLRs in intestinal epithelial cells.
基金Supported by the National Natural Science Foundation of China(No.31471663)the Qingdao Postdoctoral Application Research Project
文摘Noroviruses(NoVs) are the main cause of viral gastroenteritis outbreaks worldwide, and oysters are the most common carriers of NoV contamination and transmission. NoVs bind specifically to oyster tissues through histo-blood group antigens(HBGAs), and this facilitates virus accumulation and increases virus persistence in oysters. To investigate the interaction of HBGAs in Pacific oysters with GⅡ.4 NoV, we examined HBGAs with ELISAs and investigated binding patterns with oligosaccharide-binding assays using P particles as a model of five GⅡ.4 NoV capsids. The HBGAs in the gut and gills exhibited polymorphisms. In the gut, type A was detected(100%), whereas type Leb(91.67%) and type A(61.11%) were both observed in the gills. Moreover, we found that seasonal NoV gastroenteritis outbreaks were not significantly associated with the specific HBGAs detected in the oyster gut and gills. In the gut, we found that strain-2006 b and strain-96/96 US bound to type A and H1 but only weakly bound to type Leb; in contrast, the Camberwell and Hunter strains exhibited weak binding to types H1 and Ley, and strain-Sakai exhibited no binding to any HBGA type. In the gills, strain-96/96 US and strain-2006 b bound to type Leb but only weakly bound to type H1; strains Camberwell, Hunter, and Sakai did not bind to oyster HBGAs. Assays for oligosaccharide binding to GⅡ.4 NoV P particles showed that strain-95/96 US and strain-2006 b strongly bound to type A, B, H1, Leb, and Ley oligosaccharides, while strains Camberwell and Hunter showed weak binding ability to type H1 and Ley oligosaccharides and strain-Sakai showed weak binding ability to type Leb and Ley oligosaccharides. Our study presents new information and enhances understanding about the mechanism for NoV accumulation in oysters. Further studies of multiple NoV-tissue interactions might assist in identifying new or improved strategies for minimizing contamination, including HBGA-based attachment inhibition or depuration.
