A Shigella Effector Dampens Inflammation by Regulating Epithelial Release of Danger Signal ATP Through Production of the Lipid Mediator PtdIns5P

Puhar A, Tronchère H, Payrastre B, Nhieu GT, Sansonetti PJ.

Immunity. 2013 Dec 12;39(6):1121-31. doi: 10.1016/j.immuni.2013.11.013.

Philippe Sansonetti, MS, MD, and Andrea Puhar, PhD, MS, Institut Pasteur

Philippe Sansonetti, MS, MD, and Andrea Puhar, PhD, MS, Institut Pasteur

This study showed that in intestinal epithelial cells enteric pathogens Shigella, Salmonella and enteropathogenic Escherichia coli (EPEC) induce rapid, regulated release of the endogenous danger signal ATP as quick and early alert response to infection. ATP release was dependent on hemichannels. In the gut, elevated concentrations of extracellular ATP caused acute inflammation, which accelerated and exasperated infection-induced mucosal destruction. To evade this immune response, Shigella injected an enzyme, IpgD, into epithelial cells owing to its Type Three Secretion System. IpgD, through production of the lipid PtdIns5P, blocked hemichannels and thereby stopped ATP release in vitro and in vivo. These findings highlighted the contribution of the endogenous danger signal ATP to the immune response against bacterial infections and identified the key role of the PtdIns5P-hemichannel-extracellular ATP axis during mucosal inflammation. PMID: 24332032