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Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence

Mahdavi, Jafar; Royer, Pierre-Joseph; Sjolinder, Hong S.; Azimi, Sheyda; Self, Tim; Stoof, Jeroen; Wheldon, Lee M.; Brannstrom, Kristoffer; Wilson, Raymond; Moreton, Joanna; Moir, James W.B.; Sihlbom, Carina; Boren, Thomas; Jonssen, Ann-Beth; Soultanas, Panos; Ala'Aldeen, Dlawer A.A.

Authors

Jafar Mahdavi

Pierre-Joseph Royer

Hong S. Sjolinder

Sheyda Azimi

Tim Self

Jeroen Stoof

Lee M. Wheldon

Kristoffer Brannstrom

Raymond Wilson

Joanna Moreton

James W.B. Moir

Carina Sihlbom

Thomas Boren

Ann-Beth Jonssen

Dlawer A.A. Ala'Aldeen



Abstract

Interactions between commensal pathogens and hosts are critical for disease development but the underlying mechanisms for switching between the commensal and virulent states are unknown. We show that the human pathogen Neisseria meningitidis, the leading cause of pyogenic meningitis, can modulate gene expression via uptake of host pro-inflammatory cytokines leading to increased virulence. This uptake is mediated by type IV pili (Tfp) and reliant on the PilT ATPase activity. Two Tfp subunits, PilE and PilQ, are identified as the ligands for TNF-a and IL-8 in a glycan-dependent manner, and their deletion results in decreased virulence and increased survival in a mouse model. We propose a novel mechanism by which pathogens use the twitching motility mode of the Tfp machinery for sensing and importing host elicitors, aligning with the inflamed environment and switching to the virulent state.

Citation

Mahdavi, J., Royer, P., Sjolinder, H. S., Azimi, S., Self, T., Stoof, J., …Ala'Aldeen, D. A. (2013). Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence. Open Biology, 3, https://doi.org/10.1098/rsob.130048

Journal Article Type Article
Publication Date Oct 9, 2013
Deposit Date Jan 4, 2016
Publicly Available Date Jan 4, 2016
Journal Open Biology
Electronic ISSN 2046-2441
Publisher Royal Society, The
Peer Reviewed Peer Reviewed
Volume 3
Article Number e130048
DOI https://doi.org/10.1098/rsob.130048
Public URL http://eprints.nottingham.ac.uk/id/eprint/31165
Publisher URL http://rsob.royalsocietypublishing.org/content/3/10/130048
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Mahdavi et al 2013 Open Biology.pdf (1.7 Mb)
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Publisher Licence URL
http://creativecommons.org/licenses/by/3.0/

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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