Present address: 4225 Microbial Sciences Building, 1550 Linden Dr., Madison, WI 53706, USA.
Distinct signalling mechanisms mediate neutrophil attraction to bacterial infection and tissue injury
Article first published online: 16 JAN 2012
© 2011 Blackwell Publishing Ltd
Volume 14, Issue 4, pages 517–528, April 2012
How to Cite
Deng, Q., Harvie, E. A. and Huttenlocher, A. (2012), Distinct signalling mechanisms mediate neutrophil attraction to bacterial infection and tissue injury. Cellular Microbiology, 14: 517–528. doi: 10.1111/j.1462-5822.2011.01738.x
- Issue published online: 12 MAR 2012
- Article first published online: 16 JAN 2012
- Accepted manuscript online: 20 DEC 2011 08:37AM EST
- Received 11 October, 2011; revised 22 November, 2011; accepted 11 December, 2011.
The signals that guide neutrophils to sites of tissue injury or infection remain elusive. H2O2 has been implicated in neutrophil sensing of tissue injury and transformed cells; however, its role in neutrophil recruitment to infection has not been explored. Here, using a pharmacological inhibitor of NADPH oxidases, diphenyleneiodonium (DPI), and genetic depletion of an epithelial-specific NADPH oxidase, we show that H2O2 is not required for neutrophil detection of localized infection with the Gram-negative bacterium Pseudomonas aeruginosa. In contrast, PI3K signalling is required for neutrophil responses to both wounding and infection. In vivo imaging using a H2O2 probe detects dynamic H2O2 generation at wounds but not at infected tissue. Moreover, DPI no longer inhibits neutrophil wound attraction when P. aeruginosa is present in the media. Finally, DPI also fails to inhibit neutrophil recruitment to localized infection with the Gram-positive bacterium, Streptococcus iniae. Our findings demonstrate that different signals are involved in sensitizing neutrophils to pathogen versus non-pathogen induced tissue damage, providing a potential target to preferentially suppress non-specific immune damage without affecting the response to infection.