IL-12 is dispensable for innate and adaptive immunity against low doses of Listeria monocytogenes
IL-12 is dispensable for innate and adaptive immunity against low doses of Listeria monocytogenes
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DOI：
10.1093/intimm/11.3.325
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发表时间：
1999-03-01
影响因子：
4.4
通讯作者：
Alber, G
中科院分区：
文献类型：
--
作者：
Brombacher, F;Dorfmüller, A;Alber, G
我们研究了IL-12 p35缺陷型在不存在生物活性IL-12 p75的情况下，突变小鼠获得比野生型小鼠更高的细菌器官负荷，并且在用正常亚致死剂量的李斯特菌感染后的第一周期间死亡。此外，在感染后第2天，突变小鼠的血液IFN-γ水平显著降低。这些结果表明，在IL-12 p35缺陷型小鼠中，IFN-γ的产生受损（其对于激活巨噬细胞的杀李斯特菌效应子功能至关重要）导致针对李斯特菌的先天免疫缺陷。与IFN-γ或IFN-γ受体缺陷型小鼠（其不能抵抗非常低剂量的李斯特菌感染）相反，IL-12 p35-/-小鼠抵抗高达1000 c.f.u.用热灭活的李斯特菌再刺激的突变小鼠的脾细胞产生大量的IFN-γ，这表明在低剂量感染下，不依赖于IL-12产生足够的IFN-γ。随后用高剂量的L.单核细胞增生导致不育消除，证明了有效的记忆应答。这些结果首次证明，在低剂量的李斯特菌IL-12既不是先天性免疫的关键，也不是保护性T细胞依赖性获得性免疫的发展。
We have studied IL-12p35-deficient (IL-12p35(-/-)) mice to evaluate the role of IL-12 in resistance against Listeria monocytogenes, In the absence of bioactive IL-12p75, mutant mice acquired higher bacterial organ burden than wild-type mice and died during the first week following infection with normally sublethal doses of Listeria, Moreover, blood IFN-gamma levels were strikingly reduced in mutant mice at day 2 post-infection. These results suggest that in IL-12p35-deficient mice impaired production of IFN-gamma which is crucial for activation of listericidal effector functions of macrophages leads to defective innate immunity against Listeria, In contrast to mice deficient for IFN-gamma or IFN-gamma receptor which are unable to resist very low infection doses of Listeria, IL-12p35-/- mice resisted up to 1000 c.f.u. and were able to eliminate Listeria, Spleen cells from mutant mice re-stimulated with heat-killed Listeria produced considerable amounts of IFN-gamma, suggesting that at low dose infection sufficient IFN-gamma is produced independently of IL-12. Subsequent challenge of these immunized mice with high doses of L. monocytogenes resulted in sterile elimination demonstrating efficient memory responses. These results demonstrate for the first time that at low doses of Listeria IL-12 is neither critical for innate immunity nor for the development of protective T cell-dependent acquired immunity.