Corrêa Gladys, de A Lindenberg Carolina, Fernandes-Santos Caroline, Gandini Mariana, Petitinga Paiva Fabienne, Coutinho-Silva Robson, F Kubelka Claire
Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil.
Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil.
Immunobiology. 2016 Jul;221(7):794-802. doi: 10.1016/j.imbio.2016.02.003. Epub 2016 Feb 27.
Purinergic signaling has a crucial role in intracellular pathogen elimination. The P2X7 purinergic receptor (P2X7R), once activated by ATP, leads to pro-inflammatory responses including reactive oxygen species production. ATP can be released by injured cells, as endogenous danger signals. Dengue fever may evolve to a severe disease, leading to hypovolemic shock and coagulation dysfunctions as a result of a cytokine storm. Our aim was to evaluate the role of P2X7R activation during Dengue virus (DENV) infection. Extracellular ATP inhibited viral load in pretreated monocytes, as measured by NS1 secretion and by decrease in DENV(+) P2X7(+) cell frequencies, suggesting that P2X7R is involved in the antiviral response. Nitric oxide (NO) has anti-DENV properties and is decreased after DENV infection. NO production after ATP stimulation is abrogated by KN62 treatment, a specific P2X7R inhibitor, indicating that P2X7R likely is acting in the virus containment process. Additionally, TNF, CXCL8, CCL2 and CXCL10 factors that are associated with dengue severity were modulated by the P2X7R activation. We conclude that P2X7R is directly involved in the modulation of the antiviral and inflammatory process that occurs during DENV infection in vitro, and may have an important role in patient recovery in a first moment.
嘌呤能信号传导在细胞内病原体清除中起关键作用。P2X7嘌呤能受体（P2X7R）一旦被ATP激活，就会引发包括活性氧产生在内的促炎反应。ATP可作为内源性危险信号由受损细胞释放。登革热可能会发展为严重疾病，由于细胞因子风暴导致低血容量性休克和凝血功能障碍。我们的目的是评估P2X7R激活在登革热病毒（DENV）感染过程中的作用。通过NS1分泌以及DENV（+）P2X7（+）细胞频率的降低来衡量，细胞外ATP抑制了预处理单核细胞中的病毒载量，这表明P2X7R参与了抗病毒反应。一氧化氮（NO）具有抗DENV特性，且在DENV感染后会减少。ATP刺激后的NO产生被特异性P2X7R抑制剂KN62处理所消除，这表明P2X7R可能在病毒控制过程中起作用。此外，与登革热严重程度相关的TNF、CXCL8、CCL2和CXCL10因子受到P2X7R激活的调节。我们得出结论，P2X7R直接参与了体外DENV感染期间发生的抗病毒和炎症过程的调节，并且可能在患者早期恢复中起重要作用。
