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.
