CXCR3-/- mice mount an efficient Th1 response but fail to control Leishmania major infection
CXCR3-/- mice mount an efficient Th1 response but fail to control Leishmania major infection
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DOI：
10.1002/eji.200425422
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发表时间：
2005-02-01
影响因子：
5.4
通讯作者：
Satoskar, AR
中科院分区：
文献类型：
--
作者：
Rosas, LE;Barbi, J;Satoskar, AR
趋化因子在将白细胞募集到感染部位中起关键作用，这对于宿主防御至关重要。我们使用CXCR 3（-/-）C57 BL/6小鼠分析了CXC趋化因子受体3（CXCR 3）在皮肤利什曼病控制中的作用。我们发现，利什曼原虫感染的CXCR 3-/-小鼠安装一个有效的Th 1应答明显增加血清水平的Th 1相关的IgG 2a和显着的生产IFN-γ和IL-12的引流淋巴结细胞，限制感染的全身传播，但未能控制寄生虫复制在感染部位和发展慢性非愈合病变。此外，CXCR 3-/-小鼠不能控制皮肤L.与CXCR 3（+/+）小鼠相比，主要生长与较少的CD 4（+）和CD 8（+）T细胞以及显著较低的IFN-γ水平有关。这些结果表明，CXCR 3在宿主防御由L.少校此外，他们还建议CXCR 3-/-小鼠对L.主要是由于受损的CD 4（+）和CD 8（+）T细胞运输以及感染部位IFN-γ产生的减少，而不是由于它们不能启动寄生虫特异性Th 1应答。
Chemokines play a critical role in recruitment of leukocytes to the site of infection, which is essential for host defense. We analyzed the role of CXC chemokine receptor 3 (CXCR3) in the control of cutaneous leishmaniasis using CXCR3(-/-) C57BL/6 mice. We found that Leishmania major-infected CXCR3-/- mice mount an efficient Th1 response as evident by markedly increased serum levels of Thl-associated IgG2a and significant production of IFN-gamma and IL-12 by the draining lymph node cells, restrict systemic spread of infection, but fail to control parasite replication at the site of infection and develop chronic non-healing lesions. Furthermore, the inability of CXCR3-/- mice to control cutaneous L. major growth was associated with fewer CD4(+) and CD8(+) T cells and significantly lower levels of IFN-gamma in theirlesions as compared to CXCR3(+/+) mice. These results demonstrate that CXCR3 plays a critical role in the host defense against cutaneous leishmaniasis caused by L. major. Furthermore, they also suggest that the susceptibility of CXCR3-/- mice to L. major is due to impaired CD4(+) and CD8(+) T cell trafficking and decreased production of IFN-gamma at the site of infection rather than to their inability to mount a parasite-specific Th1 response.