本研究是與本實驗室的博士生高銘杉學長共同完成的。本人的貢獻,包括純化蛋白質、病毒接種、小鼠實驗、IL-6檢測、細菌篩選、肺液採集、電壓測量、DNA純化、PCR反應、細菌發酵以及HPLC實驗等,在本論文中均有介紹。作為共同作者,題為「Nasal colonization of Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein-induced interleukin-6 in the lung」的手稿標題和摘要作為附錄。 ;It has been reported that infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered excessive interleukin (IL)-6 signaling, leading to a myriad of biological effects including a cytokine storm that contributed to multiple organ failure in coronavirus disease 2019 (COVID-19). Using a humanized mouse model, we have demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS-CoV-2 increased IL-6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid coco-caprylate/caprate (LCC) onto Staphylococcus epidermidis (S. epidermidis)-colonized mice significantly diminished NPP-induced IL-6. Furthermore, S. epidermidis- mediated LCC fermentation to generate electricity and butyric acid that promoted bacterial colonization and activated free fatty acid receptor 2 (Ffar2), respectively. Inhibition of Ffar2 suppressed the effect of S. epidermidis plus LCC on the reduction of NPP-induced IL-6. In summary, results in this study suggest that nasal S. epidermidis may be part of the first line of defense in ameliorating a cytokine storm induced by airway infection of SARS-CoV-2.
This study has been conducted with Mr. Ming Shan Kao, a PhD student in our laboratory. My contributions including protein purification, virus inoculation, mouse experiments, Interleukin (IL)-6 assays, bacterial screening, lung fluid collection, voltage measurement, DNA purification, PCR reaction, bacterial fermentation and HPLC experiments, have been described in this thesis. As a co-author, the title and abstract of a manuscript entitled” Nasal colonization of Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein-induced interleukin-6 in the lung” have been attached as an appendix.