Yasuhide Kawamoto1, Yoshitomo Morinaga2, Yumiko Kimura1, Norihito Kaku1, Kosuke Kosai1, Naoki Uno1, Hiroo Hasegawa1, Katsunori Yanagihara1. 1. Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan. 2. Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan. Electronic address: y-morina@nagasaki-u.ac.jp.
Abstract
BACKGROUND: TNF-α plays an important role in the pathogenesis of Legionella pneumophila (Lp)-induced pneumonia. Patients undergoing anti-TNF-α therapy are at an increased risk of Lp infection. Lp infects both phagocytic and non-phagocytic cells such as airway epithelial cells; however, the role of TNF-α in airway epithelial cells is unknown. METHODS: Human airway epithelial cell line NCI-H292 was infected with Lp NUL1 strain. After infection, both intracellular growth of Lp and cell death were evaluated after treating the cells with or without TNF-α. Apoptosis was examined by performing activated caspase-3/7 staining and by using a pan-caspase inhibitor. RESULTS: Lp infected and replicated in NCI-H292 cells in a time-dependent manner, and TNF-α treatment of Lp-infected NCI-H292 cells inhibited Lp replication. Inhibitory effects of TNF-α on Lp replication were suppressed after treatment with a TNF-α-neutralizing antibody. Lp infection increased extracellular lactate dehydrogenase levels and decreased the number of living cells. Increased number of Lp-infected NCI-H292 cells showed caspase-3/7 activation, indicating they underwent apoptosis. TNF-α treatment inhibited Lp replication by increasing the apoptosis of NCI-H292 cells. CONCLUSIONS: Thus, our results suggested that airway epithelial cells were involved in the pathogenesis of Lp infection and that TNF-α played a protective role by inhibiting the intracellular replication of Lp and by increasing the apoptosis of Lp-infected airway epithelial cells. However, Lp infection should be investigated further in patients undergoing anti-TNF-α therapy who develop pneumonia.
BACKGROUND: TNF-α plays an important role in the pathogenesis of Legionella pneumophila (Lp)-induced pneumonia. Patients undergoing anti-TNF-α therapy are at an increased risk of Lp infection. Lp infects both phagocytic and non-phagocytic cells such as airway epithelial cells; however, the role of TNF-α in airway epithelial cells is unknown. METHODS:Human airway epithelial cell line NCI-H292 was infected with Lp NUL1 strain. After infection, both intracellular growth of Lp and cell death were evaluated after treating the cells with or without TNF-α. Apoptosis was examined by performing activated caspase-3/7 staining and by using a pan-caspase inhibitor. RESULTS:Lp infected and replicated in NCI-H292 cells in a time-dependent manner, and TNF-α treatment of Lp-infected NCI-H292 cells inhibited Lp replication. Inhibitory effects of TNF-α on Lp replication were suppressed after treatment with a TNF-α-neutralizing antibody. Lp infection increased extracellular lactate dehydrogenase levels and decreased the number of living cells. Increased number of Lp-infected NCI-H292 cells showed caspase-3/7 activation, indicating they underwent apoptosis. TNF-α treatment inhibited Lp replication by increasing the apoptosis of NCI-H292 cells. CONCLUSIONS: Thus, our results suggested that airway epithelial cells were involved in the pathogenesis of Lp infection and that TNF-α played a protective role by inhibiting the intracellular replication of Lp and by increasing the apoptosis of Lp-infected airway epithelial cells. However, Lp infection should be investigated further in patients undergoing anti-TNF-α therapy who develop pneumonia.
Authors: Javeed A Shah; Robyn Emery; Brian Lee; Sambasivan Venkatasubramanian; Jason D Simmons; Melanie Brown; Chi F Hung; Jan M Prins; Annelies Verbon; Thomas R Hawn; Shawn J Skerrett Journal: Mucosal Immunol Date: 2019-08-28 Impact factor: 7.313
Authors: Nikita Lad; Alice M Murphy; Cristina Parenti; Carl P Nelson; Neil C Williams; Graham R Sharpe; Philip G McTernan Journal: Clin Sci (Lond) Date: 2021-12-22 Impact factor: 6.124
Authors: Rebecca A Ward; George R Thompson; Alexandra-Chloé Villani; Bo Li; Michael K Mansour; Marcel Wuethrich; Jenny M Tam; Bruce S Klein; Jatin M Vyas Journal: J Fungi (Basel) Date: 2021-05-11