IL-4-deficient Balb/c mice resist infection with Leishmania major.
IL-4-deficient Balb/c mice resist infection with Leishmania major.
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DOI：
10.1084/jem.184.3.1127
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发表时间：
1996-09-01
期刊：
影响因子：
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通讯作者：
Solbach W
中科院分区：
文献类型：
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作者：
Kopf M;Brombacher F;Köhler G;Kienzle G;Widmann KH;Lefrang K;Humborg C;Ledermann B;Solbach W
使用在Balb/c和129 Sv背景下具有IL-4或IFN-γ R1（单突变体）和IL-4/IFN-γ R1（双突变体）基因工程缺陷的小鼠来研究硕大利什曼原虫感染的过程。与遗传抗性129 Sv野生型小鼠相反，IL-4/IFN-γ R1双突变小鼠发生胎儿疾病，寄生虫传播到内脏器官，类似于仅缺乏IFN-γ R1的小鼠。Balb/c小鼠对L.主要是通过破坏IL-4基因来抵抗感染。与纯合IL-4+/-小鼠、杂合IL-4+/-小鼠、杂合IL-4+/-动物相比，始终出现较小的病变，溃疡和坏死较少，表明可能存在基因剂量效应。这意味着IL-4应答的大小决定了疾病的严重程度。通过特征性细胞因子的定量RT-PCR评估，IL-4缺陷小鼠的CD 4 + T细胞显示受损的Th 2细胞发育。抗性的发展不能用默认的Th 1发展来解释，因为这仅在感染的非常晚期阶段观察到。此外，炎性细胞因子（例如，IL-1 α、IL- 1 β、TNF-α、IL-12）以及病变和引流淋巴结中的iNOS在不存在IL-4的情况下没有改变。
Mice with a genetically engineered deficiency for either IL-4 or IFN- gamma R1 (single mutants), and IL-4/IFN-gamma R1 (double mutants) on the Balb/c and 129Sv background were used to study the course of infection with Leishmania major. In contrast to genetically resistant 129Sv wildtype mice, IL-4/IFN-gamma R1 double mutant mice developed fetal disease with parasite dissemination to visceral organs similar to mice lacking IFN-gamma R1 only. Balb/c mice, which are exquisitely susceptible to L. major, were rendered resistant to infection by disruption of the IL-4 gene. As compared to homozygous IL-4+/- mice, heterozygous IL-4+/- mice, heterozygous IL-4+/- animals consistently developed smaller lesions with less ulceration and necrosis, indicating the likelihood of gene-dosage effects. This implicates that the magnitude of the IL-4 response determines the severity of disease. CD4+ T cells of IL-4-deficient mice showed impaired Th2 cell development, as assessed by quantitative RT-PCR of characteristic cytokines. Development of resistance is not explained by default Th1 development, because this was observed only at very late stages of infection. Moreover, the induction of inflammatory cytokines (e.g., IL-1 alpha, IL- 1 beta, TNF-alpha, IL-12) together with iNOS in the lesion and draining lymph nodes was not altered in the absence of IL-4.