Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection
Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection
复制标题
DOI：
10.1099/vir.0.053124-0
复制
发表时间：
2013-07-01
影响因子：
3.8
通讯作者：
Tripp, Ralph A.
中科院分区：
文献类型：
--
作者：
Fox, Julie M.;Sage, Leo K.;Tripp, Ralph A.
流感感染可引起肺组织吲哚胺2，3-双加氧酶(IDO)活性升高。IDO是犬尿氨酸途径中的第一步，也是限速步骤，色氨酸被还原为犬尿氨酸和其他代谢物。色氨酸的消耗和相关代谢物的产生会减弱对感染的免疫反应。用IDO抑制剂1-甲基-D-L-色氨酸(1mT)测定IDO对流感病毒感染的原发免疫应答的影响。经1mT处理后，感染A/HKx31流感病毒的C57BL/6小鼠肺组织中活化的和功能性的CD4(+)T细胞、流感特异性CD8(+)T细胞和效应记忆细胞数量增加。抑制I-DO可增加CD4(+)T细胞的Th1应答，也可增强Th17应答。这些研究表明，抑制IDO可以产生更强大的T细胞对流感病毒的反应，并提出了一种通过促进流感特异性T细胞反应来增强对流感疫苗的免疫反应的方法。
Influenza infection induces an increase in the level of indoleamine 2,3-dioxygenase (IDO) activity in the lung parenchyma. IDO is the first and rate-limiting step in the kynurenine pathway where tryptophan is reduced to kynurenine and other metabolites. The depletion of tryptophan, and production of associated metabolites, attenuates the immune response to infection. The impact of IDO on the primary immune response to influenza virus infection was determined using the IDO inhibitor 1-methyl-D,L-tryptophan (1MT). C57BL/6 mice treated with 1MT and infected with A/HKx31 influenza virus had increased numbers of activated and functional CD4(+) T-cells, influenza-specific CD8(+) T-cells and effector memory cells in the lung. Inhibition of I DO increased the Th1 response in CD4(+) T-cells as well as enhanced the Th17 response. These studies show that inhibition of IDO engenders a more robust T-cell response to influenza virus, and suggests an approach for enhancing the immune response to influenza vaccination by facilitating increased influenza-specific T-cell response.