本文旨在观察不同毒力钩端螺旋体激活THP-1细胞因子信号途径的差异,探讨天然免疫在钩端螺旋体病发病机制中的作用。将三种不同毒力钩体致病性钩端螺旋体赖型有毒株Lai株、赖型无毒株IPAV株以及非致病性钩端螺旋体Patoc型Patoc 1株与诱导后的人单核巨噬细胞株THP-1细胞相互作用，在作用后0h、2h、12h、24h、48h 收集标本，应用Real-time RT-PCR法和ELISA法检测细胞因子TNF-α、IFN-γ、IL-12、MCP-1在基因和蛋白水平的表达，同时应用Real-time RT-PCR法检测细胞表面受体TLR2、TLR4以及iNOS基因表达水平。结果发现赖型有毒株Lai株和无毒株IPAV株引起TLR4和iNOS基因表达升高，Patoc型Patoc 1株引起THP-1细胞TLR-2、TLR-4和iNOS基因表达升高。有毒株Lai株引起THP-1 TNF-α、IFN-γ、IL-12、MCP-1表达水平低于无毒株IPAV株和Patoc 1株（p<0.05）。有毒株Lai株引起较低水平细胞因子表达可能有利于其逃避宿主天然免疫反应，从而进一步在宿主体内播散繁殖。

The purpose of this study was to observe the THP-1 cytokine response induced by different virulent Leptospira strains and evaluate the role of innate immune in the pathogenesis of leptospirosis. THP-1 induced by phorbol myristoyl acetate were incubated with three different Leptospira strains, the virulent Leptospira interrogans serovar Lai type strain Lai, the avirulent L. interrogans serovar Lai type strain IPAV, and the nonpathogenic L. biflexa serovar Patoc type strain Patoc 1 respectively. Cells and supernatant infected by leptospires were collected at 0、2、12、24 and 48 hours post inoculation. The mRNA and protein levels of TNF-α、IFN-γ、IL-12、MCP-1 were quantified by real-time RT-PCR and ELISA. Meanwhile, real-time RT-PCR was used to detected mRNA levels of TLR2、TLR4 and iNOS of THP-1 infected by leptospires. It was found that Lai type strain Lai and Lai type strain IPAV can induce THP-1 TLR4 and iNOS expression in mRNA levels, but Patoc type strain Patoc 1 can induce THP-1 TLR2, TLR4 and iNOS expression in mRNA levels. The level of the THP-1 cytokine TNF-α、IFN-γ、IL-12、MCP-1 inoculation with strain Lai was lower than that inoculation with strain IPAV and strain Patoc 1 neither the level of mRNA nor protein. Thus the virulent strain Lai induces low 1evels of cytokines may be precipitate to escape of the host immune response and spreading.