Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence
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 ge...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
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Royal Society Publishing
2013
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| Online Access: | https://eprints.nottingham.ac.uk/31165/ |
| _version_ | 1848794140170518528 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Mahdavi, Jafar |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:11:27Z |
| format | Article |
| id | nottingham-31165 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:11:27Z |
| publishDate | 2013 |
| publisher | Royal Society Publishing |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-311652020-05-04T16:39:26Z https://eprints.nottingham.ac.uk/31165/ 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. 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. Royal Society Publishing 2013-10-09 Article PeerReviewed 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 and Ala'Aldeen, Dlawer A.A. (2013) Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence. Open Biology, 3 . e130048/1-e130048/15. ISSN 2046-2441 http://rsob.royalsocietypublishing.org/content/3/10/130048 doi:10.1098/rsob.130048 doi:10.1098/rsob.130048 |
| spellingShingle | 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. Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence |
| title | Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence |
| title_full | Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence |
| title_fullStr | Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence |
| title_full_unstemmed | Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence |
| title_short | Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence |
| title_sort | pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence |
| url | https://eprints.nottingham.ac.uk/31165/ https://eprints.nottingham.ac.uk/31165/ https://eprints.nottingham.ac.uk/31165/ |