Interleukin 1 participates in the development of anti-Listeria responses in normal and SCID mice.
Interleukin 1 participates in the development of anti-Listeria responses in normal and SCID mice.
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DOI：
10.1073/pnas.89.3.1011
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发表时间：
1992-02
影响因子：
11.1
通讯作者：
H. W. Rogers;K. Sheehan;L. Brunt;Steven K. DOWERt;E. Unanue;R. Schreiber
中科院分区：
文献类型：
--
作者：
H. W. Rogers;K. Sheehan;L. Brunt;Steven K. DOWERt;E. Unanue;R. Schreiber
利用带有SCID突变的T细胞和B细胞缺陷的C.B-17小鼠，我们先前已经证明存在T细胞非依赖但依赖干扰素伽马的巨噬细胞激活途径，该途径使宿主对兼性细胞内单核细胞增生性李斯特菌产生部分抵抗。这一途径在正常和SCID小鼠中都是可行的，至少由四个成分组成：干扰素γ、肿瘤坏死因子、巨噬细胞和自然杀伤细胞。在这里，我们证明，白介素1也参与这一途径，但在不同的作用部位。使用中和白介素1α和白介素1β生物活性的单抗，我们证明白介素1既不直接参与从分离的SCID自然杀伤细胞诱导干扰素伽马，也不参与来自李斯特氏菌免疫C.B-17小鼠的CD4+T细胞的抗原特异性激活。相比之下，将抗白介素1α、抗白介素1β和新获得的针对鼠I型白介素1受体的单抗注射到SCID或正常C.B-17小鼠中，可阻止动物感染李斯特菌后体内产生II类主要组织相容性复合体阳性巨噬细胞。此外，用抗白介素1混合物治疗的SCID小鼠在体内未能控制李斯特菌的生长，最终死于感染。这些结果证明，内源性产生的白介素1在依赖李斯特菌激活的体内巨噬细胞的诱导中起着特有的作用，并表明白介素1的作用不同于自然杀伤细胞来源的干扰素γ的产生。
Using T- and B-cell deficient C.B-17 mice with the scid mutation, we have previously documented the existence of a T-cell-independent but interferon gamma-dependent pathway of macrophage activation that confers upon the host partial resistance to the facultative intracellular bacterium Listeria monocytogenes. This pathway is operative in both normal and SCID mice and consists of at least four components: interferon gamma, tumor necrosis factor, macrophages, and natural killer cells. Here we demonstrate that interleukin 1 also participates in this pathway but at a different site of action. Using monoclonal antibodies that neutralize the biologic activities of interleukin 1 alpha and interleukin 1 beta, we document that interleukin 1 participates neither directly in the induction of interferon gamma from isolated SCID natural killer cells nor in the antigen-specific activation of CD4+ T cells derived from Listeria-immune C.B-17 mice. In contrast, injection of a mixture of anti-interleukin 1 alpha, anti-interleukin 1 beta, and a newly derived monoclonal antibody specific for the murine type I interleukin-1 receptor into either SCID or normal C.B-17 mice blocked the in vivo elaboration of class II major histocompatibility complex-positive macrophages after infection of the animals with Listeria. Moreover, SCID mice treated with the anti-interleukin-1 mixture failed to control the growth of Listeria in vivo and eventually succumbed to the infection. These results document that endogenously produced interleukin 1 plays an obligate role in the Listeria-dependent induction of activated macrophages in vivo and demonstrate that the action of interleukin 1 is distinct from the generation of natural killer cell-derived interferon gamma.