Investigation the role of glycerophosphodiester phosphodiesterase 2 (glpQ2) in secondary pneumococcal pneumonia after influenza virus infection

• Main Authors: Min-Jheng Lu, 呂旻錚
• Other Authors: Yi-Ping Chuang
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/03797227977518723553

碩士 === 國防醫學院 === 微生物及免疫學研究所 === 103 === Streptococcus pneumoniae is a frequent pathogen isolated from secondary bacterial pneumonia after influenza virus infection; however, the contribution of influenza virus in S. pneumoniae related community-acquired pneumonia (CAP) is often ignored. Although pneumococcal pneumonia tends to be recovered without damaging lung architectures, increased incidences of complicated CAP caused by S. pneumoniae are presented in recent years. The underlying pathogenesis is still unclear. Epidemiological analysis revealed that serotype 1, 3, 6B, 14, and 19A were correlated with the severity of pneumonia, and glpQ2 gene has been found recently to be prevalent in most of these strains. glpQ2 enhances phosphorylcholine (ChoP) expression on a 19A strain and mediated pneumococcal colonization after pulmonary infection in murine. Since the cognate receptor of ChoP, PAFR, can be upregulated by influenza virus, it suggests the influenza virus contributes to the complication of CAP. In this study, I generated a secondary pneumococcal pneumonia model after 1, 2, or 3 week after influenza virus infection. glpQ2 seemed to assist pneumococcal colonization and to trigger IL-1β production only after one week of virus infection. Although IL-1β contributed to coagulation activation, the level of tissue factor, PAI-1, and thrombin activity was not induced. S. pneumoniae infection upregulated IL-33 secretion in BALF but decreased IFN-γ production after 48 hour of infection, suggesting bacteria potentiated cytotoxicity and immune dysfunction at this time. However, it was not relevant of glpQ2 gene. Since glpQ2-mediated ChoP upregulation conferred C-reactive protein (CRP) binding, this study will further identify the downstream immune responses after CRP cognation. In conclusion, glpQ2 could assist colonization and trigger IL-1β upregulation in a secondary pneumococcal pneumonia model after one week of influenza virus infection. Next, I will modify the infection model to determine the effects of glpQ2 in immunopathogesis.