Significance of RANTES-CCR5 axis and linked downstream immunomodulation in Dengue pathogenesis: A study from Guwahati, India

RANTES-CCR5 轴及其相关下游免疫调节在登革热发病机制中的重要性:印度古瓦哈提的一项研究

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作者:Mafidul Islam, Trishna Kalita, Anjan K Saikia, Anjuma Begum, Vargab Baruah, Nidhi Singh, Raktim Borkotoky, Sujoy Bose

Abstract

We aimed to evaluate the significance of the RANTES-CCR5 axis and resulting immunomodulatory status in Dengue pathogenesis involving a Guwahati, India based population where Dengue cases have increased alarmingly. An increased CC-chemokine receptor type 5 (CCR5) messenger RNA expression and CCR5 positive cell count profile was observed in Dengue cases, the highest being in severe cases. CCR5 ligand RANTES expression was significantly decreased in Dengue cases and inversely correlated with Dengue viremia fold change in severe cases. Monocytes are involved in Dengue virus homing and replication. Its levels and activation profile were higher in Dengue cases. A hyper Th1-biased immunomodulatory profile with upregulated tumor necrosis factor-α levels, and downregulated expression of antiviral cytokine interferon-γ and key regulatory Th2 anti-inflammatory cytokine interleukin 10 was observed in severe Dengue cases compared with mild Dengue cases and controls. The results, therefore, suggest the significance of RANTES-CCR5 axis deregulation and resulting altered immunomodulation in Dengue pathogenesis, and holds prognostic and therapeutic significance.

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