Baldwin T, Sakthianandeswaren A, Curtis J M, Kumar B, Smyth G K, Foote S J, Handman E
The Walter and Eliza Hall Institute, Parkville, Victoria, Australia.
Parasite Immunol. 2007 Oct;29(10):501-13. doi: 10.1111/j.1365-3024.2007.00969.x.
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.
在传统的皮肤利什曼病小鼠模型中,通过在小鼠尾巴根部接种静止期硕大利什曼原虫前鞭毛体来引发感染。携带利什曼病抗性位点lmr1、2、3的近交系小鼠,与易感的亲本BALB/c小鼠相比,其皮损愈合更快,且能形成更有序的胶原纤维;而在抗性C57BL/6背景下携带易感位点的近交系小鼠则情况相反。在该模型中,我们发现伤口愈合而非T细胞反应在决定皮肤感染的消退中起主要作用。在此,我们在更接近人类情况的小鼠模型中展示了类似的疾病表型,即通过在耳廓严格进行皮内接种少量循环前鞭毛体。数据表明,在感染部位,先天性和适应性免疫反应协同作用以清除寄生虫,并诱导组织修复和伤口愈合。重要的是,数据显示由lmr位点控制的宿主反应在局部发挥作用以控制皮肤感染,这与在引流淋巴结中全身起作用的宿主反应不同。