Vimalanathan Selvarani, Schoop Roland, Suter Andy, Hudson James
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada V6T 2B5.
Medical Department, A. Vogel Bioforce AG, Roggwil TG, Switzerland.
Virus Res. 2017 Apr 2;233:51-59. doi: 10.1016/j.virusres.2017.03.006. Epub 2017 Mar 7.
Viral infections may predispose the airways to secondary bacterial infections that can lead to unfavorable progression of principally self-limiting illnesses. Such complicated respiratory infections include pneumonia, bronchitis, sinusitis, acute otitis media, and sepsis, which cause high morbidity and lethality. Some of the pathogenic consequences of viral infections, like the expression of bacterial adhesion receptors and the disturbance of physical barrier integrity due to inflammation, may create permissive conditions for co-infections. Influenza virus A (H3N2) is a major pathogen that causes secondary bacterial infections and inflammation that lead to pneumonia. The herbal medicine Echinacea purpurea, on the other hand, has been widely used to prevent and treat viral respiratory infections, and recent clinical data suggest that it may prevent secondary infection complications as well. We investigated the role of standardized E. purpurea (Echinaforce extract or EF) on H3N2-induced adhesion of live nontypeable Haemophilus influenzae (NTHi) and Staphylococcus aureus, along with the expression of bacterial receptors, intracellular adhesion molecule-1 (ICAM-1), fibronectin, and platelet activating factor receptor (PAFr), by BEAS-2B cells. Inflammatory processes were investigated by determining the cellular expression of IL-6 and IL-8 and the involvement of Toll-like receptor (TLR-4) and NFκB p65. We found that influenza virus A infection increased the adhesion of H. influenzae and S. aureus to bronchial epithelial cells via upregulated expression of the ICAM-1 receptor and, to some extent, of fibronectin and PAFr. Echinaforce (EF) significantly reduced the expression of ICAM-1, fibronectin, and PAFr and consequently the adhesion of both bacterial strains. EF also effectively prevented the super-expression of inflammatory cytokines by suppressing the expression of NFκB and possibly TLR-4. These results indicate that E. purpurea has the potential to reduce the risk of respiratory complications by preventing virus-induced bacterial adhesion and through the inhibition of inflammation super-stimulation (cytokine storms).
病毒感染可能使气道易发生继发性细菌感染，从而导致原本自限性疾病的不利进展。此类复杂的呼吸道感染包括肺炎、支气管炎、鼻窦炎、急性中耳炎和败血症，它们会导致高发病率和致死率。病毒感染的一些致病后果，如细菌黏附受体的表达以及炎症导致的物理屏障完整性破坏，可能为合并感染创造有利条件。甲型流感病毒（H3N2）是导致继发性细菌感染和炎症进而引发肺炎的主要病原体。另一方面，草药紫锥菊已被广泛用于预防和治疗病毒性呼吸道感染，最近的临床数据表明它也可能预防继发性感染并发症。我们研究了标准化紫锥菊（紫锥菊提取物或EF）对H3N2诱导的活的不可分型流感嗜血杆菌（NTHi）和金黄色葡萄球菌黏附的作用，以及BEAS - 2B细胞中细菌受体、细胞间黏附分子 - 1（ICAM - 1）、纤连蛋白和血小板活化因子受体（PAFr）的表达。通过测定IL - 6和IL - 8的细胞表达以及Toll样受体（TLR - 4）和NFκB p65的参与情况来研究炎症过程。我们发现甲型流感病毒感染通过上调ICAM - 1受体以及在一定程度上上调纤连蛋白和PAFr的表达，增加了流感嗜血杆菌和金黄色葡萄球菌对支气管上皮细胞的黏附。紫锥菊提取物（EF）显著降低了ICAM - 1、纤连蛋白和PAFr的表达，从而降低了两种细菌菌株的黏附。EF还通过抑制NFκB以及可能的TLR - 4的表达，有效预防了炎性细胞因子的过度表达。这些结果表明，紫锥菊有潜力通过预防病毒诱导的细菌黏附以及抑制炎症过度刺激（细胞因子风暴）来降低呼吸道并发症的风险。
