CXCR3 and IFN protein-10 in Pneumocystis pneumonia
CXCR3 and IFN protein-10 in Pneumocystis pneumonia
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DOI：
10.4049/jimmunol.177.3.1846
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Kolls, Jay K.
中科院分区：
文献类型：
--
作者：
McAllister, Florencia;Ruan, Sanbao;Kolls, Jay K.
我们以前已经表明，Tc 1 CD 8（+）T细胞在体外和体内对肺孢子虫（PC）感染的小鼠效应活性。由于这些细胞优先表达CXCR 3，因此我们研究了宿主针对PC的防御活性是否需要CXCR 3。CXCR 3缺陷但CD 4（+）T细胞完整的小鼠显示出初始延迟，但能够清除感染性攻击，表明CXCR 3信号传导对于PC的清除不是必需的。在感染的第7天，CD 4耗尽的小鼠具有由IFN-γ、IFN蛋白-10（IP-10）和IFN诱导的T细胞α-化学引诱物诱导的较低水平的单核因子，并且允许PC感染。通过腺病毒基因转移在肺中过度表达IP-10并没有加速对照小鼠的感染清除，但在CD 4（+）T细胞耗尽的小鼠中，在第28天加速了感染清除。与对照小鼠相比，这种效应与体外活化后CXCR 3（+）表达水平较高的肺中CD 8（+）T募集增加和IFN-γ分泌增加有关。这些结果表明CXCR 3趋化因子是宿主对PC防御反应的一部分，IP-10可以指导Tc 1 CD 8（+）T细胞募集到肺部，即使在没有CD 4（+）T细胞的情况下也有助于宿主对PC的防御。
We have previously shown that Tc1 CD8(+) T cells have in vitro and in vivo effector activity against Pneumocystis (PC) infection in mice. Because these cells have preferential expression of CXCR3, we investigated whether CXCR3 was required for host defense activity against PC. Mice deficient in CXCR3 but CD4(+) T cell intact, showed an initial delay but were able to clear the infectious challenge, indicating that CXCR3 signaling is not essential for clearance of PC. CD4-depleted mice had lower levels of monokine induced by IFN-gamma, IFN protein-10 (IP-10), and IFN-inducible T cell alpha-chemoattractant at day 7 of infection and are permissive to PC infection. Overexpression of IP-10 in the lungs by adenoviral gene transfer did not accelerate clearance of infection in control mice but accelerated, clearance by day 28 in mice depleted of CD4(+) T cells. This effect was associated with increased recruitment of CD8(+) T to the lungs with higher CXCR3(+) expression levels and enhanced IFN-gamma secretion upon in vitro activation compared with control mice. These results indicate that the CXCR3 chemokines are part of the host defense response to PC, and that IP-10 can direct Tc1 CD8(+) T cell recruitment to the lungs and contribute to host defense against PC even in the absence of CD4(+) T cells.