Leishmaniasis host response loci (lmr1-3) modify disease severity through a Th1/Th2-independent pathway
Leishmaniasis host response loci (lmr1-3) modify disease severity through a Th1/Th2-independent pathway
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DOI：
10.1038/sj.gene.6364042
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发表时间：
2004-03-01
影响因子：
5
通讯作者：
Handman, E
中科院分区：
文献类型：
--
作者：
Elso, CM;Roberts, LJ;Handman, E
感染硕大利什曼原虫引起的疾病的严重程度主要取决于宿主的遗传学。在抗性C57 BL/6小鼠中T辅助细胞（Th）1型免疫应答的早期诱导和在易感BALB/c小鼠中Th 2型免疫应答的早期诱导被认为分别决定治愈或疾病。我们以前绘制了三个主机响应基因座之间的C57 BL/6和BALB/c小鼠的遗传杂交，在这里，我们明确显示这些基因座的参与疾病的严重程度，使用动物同源的每个基因座。令人惊讶的是，在感染的晚期，当同类小鼠和亲本小鼠之间的疾病严重程度差异最明显时，它们的细胞因子谱与小鼠的遗传背景相关，而与疾病的严重程度无关。这表明，我们已经映射的位点是由一个独立的Th表型的机制。
The severity of disease caused by infection with Leishmania major depends critically on the genetics of the host. Early induction of T helper (Th)1-type immune responses in the resistant C57BL/6 mice and Th2-type responses in the susceptible BALB/c mice are thought to determine cure or disease, respectively. We have previously mapped three host response loci in a genetic cross between C57BL/6 and BALB/c mice, and here we show definitively the involvement of these loci in disease severity using animals congenic for each of the loci. Surprisingly, in the late stage of infection when the difference in disease severity between congenic and parental mice was most pronounced, their cytokine profile correlated with the genetic background of the mice and not with the severity of disease. This indicates that the loci that we have mapped are acting by a mechanism independent of Th phenotype.