ID: 151: Unique and overlapping roles of type I and type III interferons in influenza pathology and therapy

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• 作者：Andreas Wack¹ ; ; Sophia Davidson¹ ; Stefania Crotta¹ ; Teresa McCabe¹ ; Edith Hessel² ; Rune Hartmann³
• 刊名：Cytokine
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：76
• 期：1
• 页码：63
• 全文大小：40 K

文摘

Type I and type III interferons (IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> and IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si2.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=3eb748473e3a01b400e0a66db2acb375" title="Click to view the MathML source">位thContainer hidden">thCode">th altimg="si2.gif" overflow="scroll">w>位w>th>) are key antiviral cytokines. In addition, IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> is increasingly recognised as potentially disease-promoting in infection. We explored the roles of these IFN families in influenza infection and as anti-influenza treatment. When comparing influenza-infected 129 to C57BL/6 mouse strains, we found increased lung damage, morbidity and mortality, yet higher levels of IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th>, in 129 mice than in the more resistant C57BL/6 mice. IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> receptor deficiency in 129 mice decreased morbidity and lung damage, and ameliorated immune-mediated tissue damage, indicating that IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> levels are a host determinant of influenza severity. In contrast, the respiratory epithelial anti-influenza response was unaffected by IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> receptor deficiency, as IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si2.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=3eb748473e3a01b400e0a66db2acb375" title="Click to view the MathML source">位thContainer hidden">thCode">th altimg="si2.gif" overflow="scroll">w>位w>th> replaced IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> in these cells. Lack of IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> signalling reduced expression of the death-inducing receptor DR5 on lung epithelia and its ligand TRAIL on inflammatory monocytes, and depletion of PDCA-1+ cells or interruption of TRAIL-DR5 interaction protected infected 129 mice. Therefore, excessive IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> signalling in response to acute influenza infection may explain morbidity. Our results suggest that humans with propensity to strong IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si1.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=196248d9738c98eff79f658e73c1b662" title="Click to view the MathML source">伪尾thContainer hidden">thCode">th altimg="si1.gif" overflow="scroll">w>伪尾w>th> signalling may be at risk of severe influenza.

We assessed the implications of our results for influenza treatment, using C57BL/6 mice with a functional Mx1 allele. Treatment with either IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si13.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=1dbcd6969613dfdb7c19153f732e1f5f" title="Click to view the MathML source">伪thContainer hidden">thCode">th altimg="si13.gif" overflow="scroll">w>伪w>th>4 or IFNthmlsrc">text stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S1043466615002987&_mathId=si2.gif&_user=111111111&_pii=S1043466615002987&_rdoc=1&_issn=10434666&md5=3eb748473e3a01b400e0a66db2acb375" title="Click to view the MathML source">位thContainer hidden">thCode">th altimg="si2.gif" overflow="scroll">w>位w>th>2 prior to infection blocked influenza replication and protected against host morbidity and mortality. In contrast, outcome of IFN treatment during influenza infection was divergent. Results of IFN therapy will be presented and discussed in the context of treatment options for influenza in humans.