Torres David, Barrier Mathieu, Bihl Franck, Quesniaux Valerie J F, Maillet Isabelle, Akira Shizuo, Ryffel Bernhard, Erard François
CNRS, Laboratoire de Génétique expérimentale et moléculaire (GEM2358), F-45071 Orléans Cedex 2, France.
Infect Immun. 2004 Apr;72(4):2131-9. doi: 10.1128/IAI.72.4.2131-2139.2004.
The control of Listeria monocytogenes infection depends on the rapid activation of the innate immune system, likely through Toll-like receptors (TLR), since mice deficient for the common adapter protein of TLR signaling, myeloid differentiation factor 88 (MyD88), succumb to Listeria infection. In order to test whether TLR2 is involved in the control of infections, we compared the host response in TLR2-deficient mice with that in wild-type mice. Here we show that TLR2-deficient mice are more susceptible to systemic infection by Listeria than are wild-type mice, with a reduced survival rate, increased bacterial burden in the liver, and abundant and larger hepatic microabscesses containing increased numbers of neutrophils. The production of tumor necrosis factor, interleukin-12, and nitric oxide and the expression of the costimulatory molecules CD40 and CD86, which are necessary for the control of infection, were reduced in TLR2-deficient macrophages and dendritic cells stimulated by Listeria and were almost abolished in the absence of MyD88, coincident with the high susceptibility of MyD88-deficient mice to in vivo infection. Therefore, the present data demonstrate a role for TLR2 in the control of Listeria infection, but other MyD88-dependent signals may contribute to host resistance.
单核细胞增生李斯特菌感染的控制依赖于先天免疫系统的快速激活,可能是通过Toll样受体(TLR)实现的,因为缺乏TLR信号传导的共同衔接蛋白——髓样分化因子88(MyD88)的小鼠会死于李斯特菌感染。为了测试TLR2是否参与感染的控制,我们比较了TLR2缺陷小鼠与野生型小鼠的宿主反应。在此我们表明,TLR2缺陷小鼠比野生型小鼠更容易受到李斯特菌的全身感染,其存活率降低,肝脏中的细菌载量增加,并且含有更多中性粒细胞的丰富且更大的肝微脓肿。在受到李斯特菌刺激的TLR2缺陷巨噬细胞和树突状细胞中,控制感染所必需的肿瘤坏死因子、白细胞介素-12和一氧化氮的产生以及共刺激分子CD40和CD86的表达均降低,而在缺乏MyD88的情况下几乎完全消失,这与MyD88缺陷小鼠对体内感染的高度易感性一致。因此,目前的数据证明了TLR2在控制李斯特菌感染中的作用,但其他MyD88依赖性信号可能有助于宿主抵抗。