LEISHMANIA INFECTION IN BALB/C IL4 NEG AND IL4R NEG MICE
BALB/C IL4 NEG 和 IL4R NEG 小鼠中的利什曼原虫感染
基本信息
- 批准号:6032385
- 负责人:
- 金额:$ 16.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-05-01 至 2003-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (adapted from application abstract): Interleukin-4 (IL-4) plays an
important role in promoting the differentiation of naive T cells into IL-4-
secreting Th2 cells. The balance of Th1 (IFN) cytokine responses versus Th2
responses in vivo is thought to be involved in several infectious diseases and
allergic responses. The prototypic in vivo model used to study Th1/Th2
responses is infection with the protozoan parasite Leishmania major. Infection
of susceptible BALB/c mice induces strong IL-4 and Th2-associated cytokine
responses, but L. major infection in resistant strains of mice is associated
with a Th1 cytokine profile. The long-term goal of this research is to study
the role of IL-4 in Th2 responses, and specifically, in determining
susceptibility to L. major in BALB/c mice. To that end, genetically pure
BALB/c IL-4 and IL-4R deficient mouse strains were generated through gene-
targeting in BALB/c embryonic stem cell lines. Infection of these mice have
revealed differences in susceptibility depending on the parasite substrain and
indicated that there are alternative pathways for at least some L. major
parasite strains to escape immune mechanisms in the absence of IL-4. The goal
of the proposed research is to identify the mechanism that allows the
substrain L. major LV39 to continue to cause disease in both IL-4-/- and IL-4R
-/- mice. The hypothesis is that a factor other than IL-4 or IL-13 is induced
by L. major LV39, but not by IR173, in IL-4R -/- mice. In order to explain the
difference between anti-IL-4 treatment in vivo and the results with
genetically-deficient mice, the hypothesis is that anti-IL-4 affects Th2
responses as well as cellular infiltration. In Specific Aim 1, the cytokine
profiles induced by LV39 and IR173 infections will be characterized at the
sight of inoculation in an ear dermal model of infection. In Specific Aim 2,
the role of IL-10 compensation will be addressed by neutralizing IL-10 in vivo
and infecting BALB/c IL-10 x IL-4R -/- double knockout mice with L. major
LV39. In Specific Aim 3, the action of anti-IL-4 treatment on cellular
infiltration will be tested in a dermal infection model. These studies will
provide novel insights into the properties of different L. major parasites and
will offer alternative theories to the Th1/Th2 paradigm in general. These
studies also will lead to new interpretations of the action of anti-IL-4
treatment in vivo.
描述(改编自应用摘要):白细胞介素-4(IL-4)在细胞内起着重要的作用。
在促进幼稚T细胞分化为IL-4-
分泌Th 2细胞。Th 1(IFN)细胞因子应答与Th 2细胞因子应答的平衡
体内反应被认为与几种感染性疾病有关,
过敏反应用于研究Th 1/Th 2的原型体内模型
感染寄生虫利什曼原虫。感染
BALB/c小鼠诱导强烈的IL-4和Th 2相关细胞因子
反应,但L。耐药品系小鼠的主要感染与
Th 1型细胞因子这项研究的长期目标是研究
IL-4在Th 2应答中的作用,特别是在决定
对L.主要在BALB/c小鼠中。为了达到这个目的,
BALB/c IL-4和IL-4 R缺陷型小鼠品系通过基因重组产生。
在BALB/c胚胎干细胞系中靶向。感染这些小鼠的
揭示了依赖于寄生虫亚株的易感性差异,
表明至少有一些L.主要
寄生虫菌株逃避免疫机制在IL-4的情况下。目标
的建议研究是确定机制,使
L.亚株主要LV 39继续引起IL-4-/-和IL-4 R
-/-老鼠。假设是诱导了IL-4或IL-13以外的因子
由L.在IL-4 R-/-小鼠中,主要LV 39,而不是IR 173。为了解释
体内抗IL-4治疗与使用抗IL-4治疗的结果之间的差异
遗传缺陷小鼠,假设抗IL-4影响Th 2
反应以及细胞浸润。在特定目标1中,细胞因子
由LV 39和IR 173感染诱导的特征将在
在耳部皮肤感染模型中接种的观察。在具体目标2中,
IL-10补偿作用将通过体内中和IL-10来解决
用L.主要
LV39。在具体目标3中,抗IL-4治疗对细胞凋亡的作用被证实。
将在皮肤感染模型中测试渗透。这些研究将
提供了新的见解不同的L.主要寄生虫和
将为Th 1/Th 2范式提供替代理论。这些
研究还将导致对抗IL-4作用的新解释,
体内治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Nancy Noben-Trauth', 18)}}的其他基金
LEISHMANIA INFECTION IN BALB/C IL4 NEG AND IL4R NEG MICE
BALB/C IL4 NEG 和 IL4R NEG 小鼠中的利什曼原虫感染
- 批准号:
6510046 - 财政年份:2001
- 资助金额:
$ 16.1万 - 项目类别:
CYTOKINES IN IMMUNE CONTROL OF ENDOGENOUS TUMORS
细胞因子对内源性肿瘤的免疫控制
- 批准号:
2109683 - 财政年份:1995
- 资助金额:
$ 16.1万 - 项目类别:
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