GRI/IRG (EA4517), Immunopathology and infectious diseases research grouping, University of La Reunion, CHU and CYROI research centres, St-Denis, La Reunion, France.
Virol J. 2012 Dec 19;9:313. doi: 10.1186/1743-422X-9-313.
Infection with Chikungunya alphavirus (CHIKV) can cause severe arthralgia and chronic arthritis in humans with persistence of the virus in perivascular macrophages of the synovial membrane by mechanisms largely ill-characterized.
We herein analysed the innate immune response (cytokine and programmed cell death) of RAW264.7 mouse macrophages following CHIKV infection. We found that the infection was restrained to a small percentage of cells and was not associated with a robust type I IFN innate immune response (IFN-α4 and ISG56). TNF-α, IL-6 and GM-CSF expression were upregulated while IFN-γ, IL-1α, IL-2, IL-4, IL-5, IL-10 or IL-17 expression could not be evidenced prior to and after CHIKV exposure. Although CHIKV is known to drive apoptosis in many cell types, we found no canonical signs of programmed cell death (cleaved caspase-3, -9) in infected RAW264.7 cells.
These data argue for the capacity of CHIKV to infect and drive a specific innate immune response in RAW264.7 macrophage cell which seems to be polarized to assist viral persistence through the control of apoptosis and IFN signalling.
基孔肯雅热病毒（CHIKV）感染可导致人类严重的关节痛和慢性关节炎，病毒通过机制在很大程度上仍未被充分阐明，潜伏在滑膜的血管周围巨噬细胞中。
我们在此分析了 RAW264.7 小鼠巨噬细胞感染 CHIKV 后的先天免疫反应（细胞因子和程序性细胞死亡）。我们发现，感染局限于一小部分细胞，并且与强大的 I 型 IFN 先天免疫反应（IFN-α4 和 ISG56）无关。TNF-α、IL-6 和 GM-CSF 的表达上调，而 IFN-γ、IL-1α、IL-2、IL-4、IL-5、IL-10 或 IL-17 的表达在 CHIKV 暴露前后均无法证实。虽然 CHIKV 已知可诱导许多细胞类型的细胞凋亡，但我们在感染的 RAW264.7 细胞中未发现典型的程序性细胞死亡（裂解的 caspase-3、-9）迹象。
这些数据表明 CHIKV 有能力感染并在 RAW264.7 巨噬细胞中驱动特定的先天免疫反应，这种反应似乎通过控制细胞凋亡和 IFN 信号转导来促进病毒的持续存在。
