The human intestinal tract is home to an enormous bacterial flora. The host defense against microorganisms can be divided into innate and adaptive immunity. The former is the most immediate line of response to immunol...The human intestinal tract is home to an enormous bacterial flora. The host defense against microorganisms can be divided into innate and adaptive immunity. The former is the most immediate line of response to immunologic challenges presented by bacteria, viruses, and fungi. The mucosal immune system has evolved to balance the need to respond to pathogens while co-existing with commensal bacteria and food antigens. In inflammatory bowel disease （IBD）, this hyporesponsiveness or tolerance breaks down and inflammation supervenes driven by the intestinal microbial flora. Bacteria contain compounds and are recognized by a variety of receptors, including Toll-like receptors （TLRs） and NODs （a family of intracellular bacterial sensors） and are potent stimuli of innate immune responses. Several mutations in these receptors have been associated with development of IBD.展开更多
Hepatitis C virus （HCV） needs to tightly manipulate host defences in order to establish infection. The innate immune response slows down viral replication by activating cytokines such as the type Ⅰ interferons （I...Hepatitis C virus （HCV） needs to tightly manipulate host defences in order to establish infection. The innate immune response slows down viral replication by activating cytokines such as the type Ⅰ interferons （IFN-α/ β）, which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. HCV has therefore developed a number of countermeasures to stay ahead of the IFN system. Here, I will attempt to summarize the current state of research regarding IFN responses against HCV and the viral escape strategies. Particular emphasis will be put on the newly discovered mechanisms HCV employs to avoid the induction of IFN in infected cells.展开更多
Signal transducers and activators of transcription 3 (STAT3) play an important role in various autoimmune disorders including inflammatory bowel disease (IBD). Recent studies have revealed that STAT3 activation plays ...Signal transducers and activators of transcription 3 (STAT3) play an important role in various autoimmune disorders including inflammatory bowel disease (IBD). Recent studies have revealed that STAT3 activation plays distinctly different roles between innate immune responses and acquired immune responses in colitis. STAT3-mediated activation of acquired immune re-sponses plays a pathogenic role in colitis by enhancing the survival of pathogenic T cells. In contrast, STAT3-mediated activation of innate responses contributes to the suppression of colitis. This review will summarize the current understanding of the roles of STAT3 in IBD and the potential of targeting STAT3 for the treatment of IBD, emphasizing recent observations.展开更多
Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overl...Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage. Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes, will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating howthe disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.展开更多
文摘The human intestinal tract is home to an enormous bacterial flora. The host defense against microorganisms can be divided into innate and adaptive immunity. The former is the most immediate line of response to immunologic challenges presented by bacteria, viruses, and fungi. The mucosal immune system has evolved to balance the need to respond to pathogens while co-existing with commensal bacteria and food antigens. In inflammatory bowel disease （IBD）, this hyporesponsiveness or tolerance breaks down and inflammation supervenes driven by the intestinal microbial flora. Bacteria contain compounds and are recognized by a variety of receptors, including Toll-like receptors （TLRs） and NODs （a family of intracellular bacterial sensors） and are potent stimuli of innate immune responses. Several mutations in these receptors have been associated with development of IBD.
文摘Hepatitis C virus （HCV） needs to tightly manipulate host defences in order to establish infection. The innate immune response slows down viral replication by activating cytokines such as the type Ⅰ interferons （IFN-α/ β）, which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. HCV has therefore developed a number of countermeasures to stay ahead of the IFN system. Here, I will attempt to summarize the current state of research regarding IFN responses against HCV and the viral escape strategies. Particular emphasis will be put on the newly discovered mechanisms HCV employs to avoid the induction of IFN in infected cells.
文摘Signal transducers and activators of transcription 3 (STAT3) play an important role in various autoimmune disorders including inflammatory bowel disease (IBD). Recent studies have revealed that STAT3 activation plays distinctly different roles between innate immune responses and acquired immune responses in colitis. STAT3-mediated activation of acquired immune re-sponses plays a pathogenic role in colitis by enhancing the survival of pathogenic T cells. In contrast, STAT3-mediated activation of innate responses contributes to the suppression of colitis. This review will summarize the current understanding of the roles of STAT3 in IBD and the potential of targeting STAT3 for the treatment of IBD, emphasizing recent observations.
基金Portuguese Foundation for Science and Technology and Calouste Gulbenkian Foundation
文摘Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage. Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes, will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating howthe disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.
