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Poly I:C stimulation in-vitro as a marker for an antiviral response in different cell types generated from Buffalo (Bubalus bubalis).
Molecular Immunology ( IF 3.6 ) Pub Date : 2020-03-19 , DOI: 10.1016/j.molimm.2020.03.004
Ashutosh Vats,Devika Gautam,Jitendra Maharana,Jatinder Singh Chera,Sushil Kumar,Pramod K Rout,Dirk Werling,Sachinandan De

The innate immune system is activated upon virus invasion of a host cell by recognizing viral component, such as dsRNA through specific receptors, resulting in the production of type- I IFNs, which confer an antiviral state within the invaded as well as surrounding cells. In the present study, fibroblast, monocyte and macrophage cells derived from water Buffalo (Bubalus bubalis) were exposed to a synthetic dsRNA analogue, poly I:C to mimic viral invasion in each cell type. Recognition of poly I:C through cytosolic helicase receptors RIG-I and MDA5 molecule lead to the activation of the RLR pathway, subsequently activating the MAVS-IRF3/7 cascade and the production of antiviral effector molecule like IFNβ and ISGs. Within the different cell types, we identified variability in RLR receptor and IFNβ expression after poly I:C administration. Fibroblasts responded quickly and strongly with IFNβ production, followed by macrophages and monocytes. Despite absolute expression variability among different cell types the expression trend of RLRs pathway genes were similar. Length of poly I:C molecule also influence IFNβ expression in response of RLR pathway. Short (LMW) poly I:C induce stronger IFN-β expression in myeloid (macrophage and monocyte) cells. In contrast long (HMW) poly I:C preferably elicit higher IFNβ expression in non-myeloid (fibroblast) cell. Therefore, MDA5 and RIG-1 plays an indispensable role in eliciting antiviral response in non- immune (fibroblast) host cell. Thus, stimulation of RLR pathway with suitable and potentially cell-type specific agonist molecules successfully elicit antiviral state in the host animal, with fibroblasts conferring a stronger antiviral state compared with the monocytes and macrophages.

中文翻译:

Poly I:C体外刺激作为水牛(Bubalus bubalis)产生的不同细胞类型中抗病毒应答的标志物。

通过识别病毒成分(例如通过特定受体的dsRNA)感染宿主细胞后,先天免疫系统被激活,从而导致产生I型干扰素,从而在被入侵的细胞以及周围细胞中赋予抗病毒状态。在本研究中,将源自水牛(Bubalus bubalis)的成纤维细胞,单核细胞和巨噬细胞暴露于合成的dsRNA类似物poly I:C,以模拟每种细胞类型中的病毒入侵。通过胞质解旋酶受体RIG-1和MDA5分子识别多聚I:C导致RLR通路的激活,随后激活MAVS-IRF3 / 7级联并产生抗病毒效应分子,如IFNβ和ISGs。在不同的细胞类型中,我们确定了多I:C给药后RLR受体和IFNβ表达的变异性。成纤维细胞对IFNβ的产生反应迅速而强烈,其次是巨噬细胞和单核细胞。尽管不同细胞类型之间存在绝对表达差异,但RLRs通路基因的表达趋势相似。聚I:C分子的长度也影响RLR途径响应中的IFNβ表达。短(LMW)聚I:C在髓样(巨噬细胞和单核细胞)细胞中诱导较强的IFN-β表达。相反,长(HMW)聚I:C优选在非骨髓(成纤维细胞)细胞中引起更高的IFNβ表达。因此,MDA5和RIG-1在引发非免疫(成纤维细胞)宿主细胞中的抗病毒应答中起着不可或缺的作用。因此,用合适且可能具有细胞类型的特异性激动剂分子刺激RLR途径可成功在宿主动物中引发抗病毒状态,
更新日期:2020-03-19
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