Differential roles of Toll-like receptors 2 and 4 in in vitro responses of macrophages to Legionella pneumophila
Differential roles of Toll-like receptors 2 and 4 in in vitro responses of macrophages to Legionella pneumophila
复制标题
DOI：
10.1128/iai.73.1.352-361.2005
复制
发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Saito, A
中科院分区：
文献类型：
--
作者：
Akamine, M;Higa, F;Saito, A
利用TLR2缺陷（TLR2(-/-)）、TLR4（-/-）和野生型（WT）同窝（C57BL/6 × 129Sv）小鼠骨髓源性巨噬细胞和树突状细胞，研究toll样受体（TLRs）在嗜肺军团菌（一种革兰氏阴性兼性胞内细菌）先天免疫中的作用。与WT和TLR4（-/-）巨噬细胞相比，TLR2（-/-）巨噬细胞内嗜肺乳杆菌的细胞内生长增强。WT和tlr缺陷小鼠树突状细胞内的细菌生长没有差异。与WT和TLR4-/-巨噬细胞相比，TLR2-/-巨噬细胞感染嗜肺乳杆菌后产生的白细胞介素-12p40 （IL-12p40）和IL-10减少。嗜肺乳杆菌dotO突变体不能在巨噬细胞内繁殖，其诱导巨噬细胞分泌IL-12p40、IL-10和肿瘤坏死因子α的效果与活毒菌株相似。WT及其突变体对细菌的细胞病变作用的易感性没有差异。嗜肺乳杆菌超声裂解液诱导巨噬细胞产生IL-12p40，但TLR2（-/-）巨噬细胞产生IL-12p40的能力明显低于WT和TLR4（-/-）巨噬细胞。用蛋白酶K和加热处理嗜肺乳杆菌的超声裂解液并没有消除tlr2依赖性IL-12p40的产生。我们的研究结果表明，TLR2而不是TLR4参与了小鼠对嗜肺乳杆菌的先天免疫，尽管其他tlr也可能有助于对该生物的先天免疫。
The role of Toll-like receptors (TLRs) in innate immunity to Legionella pneumophila, a gram-negative facultative intracellular bacterium, was studied by using bone marrow-derived macrophages and dendritic cells from TLR2-deficient (TLR2(-/-)), TLR4(-/-), and wild-type (WT) littermate (C57BL/6 x 129Sv) mice. Intracellular growth of L. pneumophila was enhanced within TLR2(-/-) macrophages compared to WT and TLR4(-/-) macrophages. There was no difference in the bacterial growth within dendritic cells from WT and TLR-deficient mice. Production of interieukin-12p40 (IL-12p40) and IL-10 after infection with L. pneumophila was attenuated in TLR2-/- macrophages compared to WT and TLR4-/- macrophages. Induction of IL-12p40, IL-10, and tumor necrosis factor alpha secretion from macrophages by the L. pneumophila dotO mutant, which cannot multiply within macrophages, and heat-killed bacteria, was similar to that caused by a viable virulent strain. There was no difference between the WT and its mutants in susceptibility to the cytopathic effect of bacteria. An L. pneumophila sonicated lysate induced IL-12p40 production by macrophages, but that of TLR2(-/-) macrophages was significantly lower than those of WT and TLR4(-/-) macrophages. Treatment of L. pneumophila sonicated lysate with proteinase K and heating did not abolish TLR2-dependent IL-12p40 production. Our results show that TLR2, but not TLR4, is involved in murine innate immunity against L. pneumophila, although other TLRs may also contribute to innate immunity against this organism.