Wound healing response is a major contributor to the severity of cutaneous leishmaniasis in the ear model of infection
Wound healing response is a major contributor to the severity of cutaneous leishmaniasis in the ear model of infection
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DOI：
10.1111/j.1365-3024.2007.00969.x
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发表时间：
2007-10-01
影响因子：
2.2
通讯作者：
Handman, E.
中科院分区：
文献类型：
--
作者：
Baldwin, T.;Sakthianandeswaren, A.;Handman, E.
在传统的小鼠皮肤利什曼病模型中，在尾巴底部感染固定期利什曼原虫原鞭毛菌，遗传利什曼病抗性位点lmr1、2、3的小鼠比易感亲代BALB/c小鼠更快地治愈了它们的病变，并形成了更多有序的胶原纤维，而携带耐药C57BL/6易感位点的基因小鼠则相反。在该模型中，我们发现伤口愈合而不是T细胞反应在决定皮肤感染的解决中起主要作用。在这里，我们在小鼠模型中显示了类似的疾病表型，更接近于人类的情况，即严格的耳廓皮内感染，伴有少量的偏环性前乳突菌。数据表明，在感染部位，先天免疫和适应性免疫反应协同作用，清除寄生虫，诱导组织修复和伤口愈合。重要的是，这些数据表明，由lmr位点控制的宿主反应，其局部作用于控制皮肤感染，与在引流淋巴结中系统操作的宿主反应不同。
In the conventional mouse model for cutaneous leishmaniasis involving infection with stationary phase Leishmania major promastigotes at the base of the tail, mice congenic for leishmaniasis resistance loci designated lmr1,2,3 cured their lesions more rapidly and laid down more ordered collagen fibres than the susceptible parental BALB/c mice, while the opposite was the case for the congenic mice carrying the susceptibility loci on the resistant C57BL/6 background. In that model, we showed that wound healing and not T cell responses played a major role in determining the resolution of skin infection. Here, we show a similar disease phenotype in the mouse model that mimics more closely the situation in humans, that is, strictly intradermal infection in the ear pinna with small numbers of metacyclic promastigotes. The data show that at the site of infection the innate and adaptive immune responses act in concert to clear parasites, and induce tissue repair and wound healing. Importantly, the data show that the host responses controlled by the lmr loci, which act locally to control infection in the skin, are distinct from the host responses operating systemically in the draining lymph node.