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The Capacity of Pneumococcus to Stimulate Macrophage NF-κB Activity Dictates the Severity of Adult Pneumococcal Pneumonia
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A7579 - The Capacity of Pneumococcus to Stimulate Macrophage NF-κB Activity Dictates the Severity of Adult Pneumococcal Pneumonia
Author Block: S. Ideguchi1, K. Yamamoto1, S. Ide1, T. Takazono1, T. Saijo1, Y. Imamura1, T. Miyazaki1, K. Yanagihara2, Y. Fukuda3, S. Nakamura4, B. Chang5, F. T. Coleman6, J. P. Mizgerd6, H. Mukae1; 1Second Department of Internal Medicine, Nagasaki University Hospital, Nagasaki, Japan, 2Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan, 3Department of Respiratory Medicine, Sasebo City General Hospital, Sasebo, Japan, 4Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan, 5Department of Bacteriology Ⅰ, National Institute of Infectious Disease, Tokyo, Japan, 6Pulmonary Center, Boston University School of Medicine, Boston, MA, United States.
RATIONALE: Alveolar macrophage is the crucial, first line of defense against pneumococcus in the lungs, inducing innate immune response via activation of a transcription factor, nuclear factor-kappa B (NF-κB). The present study aims to clarify whether the phenotypes of adult pneumococcal pneumonia are dictated by the capacity of pneumococci to activate macrophage NF-κB.
METHODS: Streptococcus pneumoniae clinical isolates were collected from adult (age > 20 years) patients with pneumococcal pneumonia, who were admitted in two tertiary hospitals in Japan from January 2011 to December 2016. Those isolates were used to stimulate clonal cell lines derived from mouse macrophage RAW264.7 cells transduced with lenti-virus that reports NF-κB-mediated gene transcription (J Infect Dis 216:425-435, 2017). The NF-κB levels, activated by the different pneumococcal isolates, were measured as percentage of the control, which was monitored in terms of the luciferase luminescence of cells stimulated by LPS. The phenotypes of pneumonia (severity, mortality, blood culture, and chest radiograph pattern) were assessed and compared between two groups: low NF-κB activators (n = 25) and high NF-κB activators (n = 25), separated by a median line of NF-κB activities.
RESULTS: A total of 50 adult patients with pneumonia (median age of 68 years, 76 % male) were included in the study. Positive pneumococcal blood culture was detected in 18 % (n = 9), and the average of systemic inflammatory response syndrome (SIRS) score was 2.1 in patients with pneumonia. Severe pneumonia, determined by the pneumonia severity index (PSI) was seen in 72 % (n = 36), and the mortality rate was 6.0 % (n = 3). Comparing the pneumonia phenotypes between the low NF-κB activator group and high NF-κB activator group, the population having bacteremia (24 % vs 12 %), PSI score ≥ IV (80 % vs 68 %), and SIRS score ≥ 2 (80 % vs 52 %, p = 0.019) was higher in the low NF-κB activator group.
CONCLUSIONS: Pneumococcal isolates that stimulate macrophage to induce low NF-κB activation, likely lead to a severe and bacteremic pneumonia in adults.
Author Block: S. Ideguchi1, K. Yamamoto1, S. Ide1, T. Takazono1, T. Saijo1, Y. Imamura1, T. Miyazaki1, K. Yanagihara2, Y. Fukuda3, S. Nakamura4, B. Chang5, F. T. Coleman6, J. P. Mizgerd6, H. Mukae1; 1Second Department of Internal Medicine, Nagasaki University Hospital, Nagasaki, Japan, 2Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan, 3Department of Respiratory Medicine, Sasebo City General Hospital, Sasebo, Japan, 4Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan, 5Department of Bacteriology Ⅰ, National Institute of Infectious Disease, Tokyo, Japan, 6Pulmonary Center, Boston University School of Medicine, Boston, MA, United States.
RATIONALE: Alveolar macrophage is the crucial, first line of defense against pneumococcus in the lungs, inducing innate immune response via activation of a transcription factor, nuclear factor-kappa B (NF-κB). The present study aims to clarify whether the phenotypes of adult pneumococcal pneumonia are dictated by the capacity of pneumococci to activate macrophage NF-κB.
METHODS: Streptococcus pneumoniae clinical isolates were collected from adult (age > 20 years) patients with pneumococcal pneumonia, who were admitted in two tertiary hospitals in Japan from January 2011 to December 2016. Those isolates were used to stimulate clonal cell lines derived from mouse macrophage RAW264.7 cells transduced with lenti-virus that reports NF-κB-mediated gene transcription (J Infect Dis 216:425-435, 2017). The NF-κB levels, activated by the different pneumococcal isolates, were measured as percentage of the control, which was monitored in terms of the luciferase luminescence of cells stimulated by LPS. The phenotypes of pneumonia (severity, mortality, blood culture, and chest radiograph pattern) were assessed and compared between two groups: low NF-κB activators (n = 25) and high NF-κB activators (n = 25), separated by a median line of NF-κB activities.
RESULTS: A total of 50 adult patients with pneumonia (median age of 68 years, 76 % male) were included in the study. Positive pneumococcal blood culture was detected in 18 % (n = 9), and the average of systemic inflammatory response syndrome (SIRS) score was 2.1 in patients with pneumonia. Severe pneumonia, determined by the pneumonia severity index (PSI) was seen in 72 % (n = 36), and the mortality rate was 6.0 % (n = 3). Comparing the pneumonia phenotypes between the low NF-κB activator group and high NF-κB activator group, the population having bacteremia (24 % vs 12 %), PSI score ≥ IV (80 % vs 68 %), and SIRS score ≥ 2 (80 % vs 52 %, p = 0.019) was higher in the low NF-κB activator group.
CONCLUSIONS: Pneumococcal isolates that stimulate macrophage to induce low NF-κB activation, likely lead to a severe and bacteremic pneumonia in adults.
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