TY - JOUR
T1 - The innate immune molecule, NOD1, regulates direct killing of Helicobacter pylori by antimicrobial peptides
AU - Grubman, Alexandra
AU - Liaskos, Maria
AU - Viala, Jerome
AU - Allison, Cody Charles
AU - Badea, Luminita
AU - Karrar, Abdulgader
AU - Boneca, Ivo G
AU - Le Bourhis, Lionel
AU - Reeve, Shane Bernadine
AU - Smith, Alexander Ian
AU - Hartland, Elizabeth Louise
AU - Philpott, Dana J
AU - Ferrero, Richard Louis
PY - 2010
Y1 - 2010
N2 - Summary The cytosolic innate immune molecule, NOD1, recognizes peptidoglycan (PG) delivered to epithelial cells via the Helicobacter pyloricag pathogenicity island (cagPAI), and has been implicated in host defence against cagPAI(+)H. pylori bacteria. To further clarify the role of NOD1 in host defence, we investigated NOD1-dependent regulation of human beta-defensins (DEFBs) in two epithelial cell lines. Our findings identify that NOD1 activation, via either cagPAI(+) bacteria or internalized PG, was required for DEFB4 and DEFB103 expression in HEK293 cells. To investigate cell type-specific induction of DEFB4 and DEFB103, we generated stable NOD1 knockdown (KD) and control AGS cells. Reporter gene assay and RT-PCR analyses revealed that only DEFB4 was induced in a NOD1-/cagPAI-dependent fashion in AGS cells. Moreover, culture supernatants from AGS control, but not AGS NOD1 KD cells, stimulated with cagPAI(+)H. pylori, significantly reduced H. pylori bacterial numbers. siRNA studies confirmed that human beta-defensin 2 (hBD-2), but not hBD-3, contributes to the antimicrobial activity of AGS cell supernatants against H. pylori. This study demonstrates for the first time the involvement of NOD1 and hBD-2 in direct killing of H. pylori bacteria by epithelial cells and confirms the importance of NOD1 in host defence mechanisms against cagPAI(+)H. pylori infection.
AB - Summary The cytosolic innate immune molecule, NOD1, recognizes peptidoglycan (PG) delivered to epithelial cells via the Helicobacter pyloricag pathogenicity island (cagPAI), and has been implicated in host defence against cagPAI(+)H. pylori bacteria. To further clarify the role of NOD1 in host defence, we investigated NOD1-dependent regulation of human beta-defensins (DEFBs) in two epithelial cell lines. Our findings identify that NOD1 activation, via either cagPAI(+) bacteria or internalized PG, was required for DEFB4 and DEFB103 expression in HEK293 cells. To investigate cell type-specific induction of DEFB4 and DEFB103, we generated stable NOD1 knockdown (KD) and control AGS cells. Reporter gene assay and RT-PCR analyses revealed that only DEFB4 was induced in a NOD1-/cagPAI-dependent fashion in AGS cells. Moreover, culture supernatants from AGS control, but not AGS NOD1 KD cells, stimulated with cagPAI(+)H. pylori, significantly reduced H. pylori bacterial numbers. siRNA studies confirmed that human beta-defensin 2 (hBD-2), but not hBD-3, contributes to the antimicrobial activity of AGS cell supernatants against H. pylori. This study demonstrates for the first time the involvement of NOD1 and hBD-2 in direct killing of H. pylori bacteria by epithelial cells and confirms the importance of NOD1 in host defence mechanisms against cagPAI(+)H. pylori infection.
UR - http://www3.interscience.wiley.com/cgi-bin/fulltext/123221341/PDFSTART
U2 - 10.1111/j.1462-5822.2009.01421.x
DO - 10.1111/j.1462-5822.2009.01421.x
M3 - Article
SN - 1462-5814
VL - 12
SP - 626
EP - 639
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 5
ER -