CD209,a transmembrane lectin belonging to the C-type lectin family,can recognize carbohydrates on the surface of host cells and invading pathogens,and play an important role in cell adhesion and migration,pathogen rec...CD209,a transmembrane lectin belonging to the C-type lectin family,can recognize carbohydrates on the surface of host cells and invading pathogens,and play an important role in cell adhesion and migration,pathogen recognition and immune activation.Although well characterized in mammals,CD209 is still under-researched in fish.Here,we report a CD209-like gene,which was named SsCD209like,in black rockfish Sebastes schlegelii,and analyzed its structure features,expression patterns and ligand-binding activities.SsCD209like displays structural similarities to mammalian CD209s,with a cytosolic tail at N-terminus,a transmembrane region and an extracellular part containing a neck region and a CRD at C-terminus.The extracellular region and the neck region of SsCD-209like can both form dimers,which is different with the tetramer in human homologue.This result demonstrates the multimerization of CD209 homologue in fish for the first time.The EPN motif,a functional motif participating in sugar binding and affinity determination,is conserved in the CRD of SsCD209like,which is consistent with the higher binding strength of this lectin to L-fucose,D-GlcNAc and D-mannose.The binding of SsCD209like to different bacteria strains and bacteria-derived pathogen associated molecular patterns(PAMPs)are also observed in a dose-dependent manner.Results in this study show the sequence and structure features of SsCD209like and demonstrate its binding properties as a pathogen recognition receptor,which promotes our understanding of CD209 homologues in fish and provides basis for more in-depth studies of this molecule in the future.展开更多
Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive imm...Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.展开更多
Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells...Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells,the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A deficiency in MDA5,RIG-Ⅰ or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication.The expression of the type I/III interferon(IFN) during infection was impaired in MDA5;and MAVS;,but not in RIG-Ⅰ;,when compared to wild type (WT) cells.The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2),the cellular entry receptor for SARS-CoV-2,was approximately 2.5-fold higher in RIG-Ⅰ;than WT cells.These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor,IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-Ⅰ in epithelial cells.展开更多
The immune responses play a profound role in the progression of lung lesions in both infectious and non-infectious diseases.Dendritic cells,as the"frontline"immune cells responsible for antigen presentation,...The immune responses play a profound role in the progression of lung lesions in both infectious and non-infectious diseases.Dendritic cells,as the"frontline"immune cells responsible for antigen presentation,set up a bridge between innate and adaptive immunity in the course of these diseases.Among the receptors equipped in dendritic cells,Toll-like re-ceptors are a group of specialized receptors as one type of pattern recognition receptors,capable of sensing environmental signals including invading pathogens and self-antigens.Toll-like receptor 4,a pivotal member of the Toll-like receptor family,was formerly recognized as a receptor sensitive to the outer membrane component lipopolysaccharide derived from Gram-negative bacteria,triggering the subsequent response.Moreover,its other essential roles in immune responses have drawn significant attention in the past decade.A better under-standing of the implication of Toll-like receptor 4 in dendritic cells could contribute to the management of pulmonary diseases including pneumonia,pulmonary tuberculosis,asthma,acutelung injury,and lung cancer.展开更多
基金financially supported by the National Natural Science Foundation of China (No.32002422)the Natural Science Foundation of Shandong Province (No.ZR 2020QC212)+4 种基金the Young Experts of Taishan Scholars (No.tsqn201909130)the Shandong Technical System of Fish Industry (No. SDAIT-12-03)the Science and Technology Support Plan for Youth Innovation of Colleges and Universities in Shandong Province (No. 2019KJF003)the Breeding Plan of Shandong Provincial Qingchuang Research Team (2019)the Advanced Talents Foundation of QAU Grant (No. 663-1120023)
文摘CD209,a transmembrane lectin belonging to the C-type lectin family,can recognize carbohydrates on the surface of host cells and invading pathogens,and play an important role in cell adhesion and migration,pathogen recognition and immune activation.Although well characterized in mammals,CD209 is still under-researched in fish.Here,we report a CD209-like gene,which was named SsCD209like,in black rockfish Sebastes schlegelii,and analyzed its structure features,expression patterns and ligand-binding activities.SsCD209like displays structural similarities to mammalian CD209s,with a cytosolic tail at N-terminus,a transmembrane region and an extracellular part containing a neck region and a CRD at C-terminus.The extracellular region and the neck region of SsCD-209like can both form dimers,which is different with the tetramer in human homologue.This result demonstrates the multimerization of CD209 homologue in fish for the first time.The EPN motif,a functional motif participating in sugar binding and affinity determination,is conserved in the CRD of SsCD209like,which is consistent with the higher binding strength of this lectin to L-fucose,D-GlcNAc and D-mannose.The binding of SsCD209like to different bacteria strains and bacteria-derived pathogen associated molecular patterns(PAMPs)are also observed in a dose-dependent manner.Results in this study show the sequence and structure features of SsCD209like and demonstrate its binding properties as a pathogen recognition receptor,which promotes our understanding of CD209 homologues in fish and provides basis for more in-depth studies of this molecule in the future.
基金Supported by Shenzhen Medical Research Fund,No.D2301010Shenzhen Science and Technology Program,No.RCYX20231211090346060。
文摘Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.
基金supported by a National Institutes of Health grant (No. R01AI132526)a UConn Health Startup fund to Wang P。
文摘Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells,the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A deficiency in MDA5,RIG-Ⅰ or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication.The expression of the type I/III interferon(IFN) during infection was impaired in MDA5;and MAVS;,but not in RIG-Ⅰ;,when compared to wild type (WT) cells.The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2),the cellular entry receptor for SARS-CoV-2,was approximately 2.5-fold higher in RIG-Ⅰ;than WT cells.These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor,IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-Ⅰ in epithelial cells.
基金supported by the National Natural Science Foundation of China,China (No.81970016,81870039).
文摘The immune responses play a profound role in the progression of lung lesions in both infectious and non-infectious diseases.Dendritic cells,as the"frontline"immune cells responsible for antigen presentation,set up a bridge between innate and adaptive immunity in the course of these diseases.Among the receptors equipped in dendritic cells,Toll-like re-ceptors are a group of specialized receptors as one type of pattern recognition receptors,capable of sensing environmental signals including invading pathogens and self-antigens.Toll-like receptor 4,a pivotal member of the Toll-like receptor family,was formerly recognized as a receptor sensitive to the outer membrane component lipopolysaccharide derived from Gram-negative bacteria,triggering the subsequent response.Moreover,its other essential roles in immune responses have drawn significant attention in the past decade.A better under-standing of the implication of Toll-like receptor 4 in dendritic cells could contribute to the management of pulmonary diseases including pneumonia,pulmonary tuberculosis,asthma,acutelung injury,and lung cancer.
