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

Jafar Mahdavi; Pierre-Joseph Royer; Hong S Sjölinder; Sheyda Azimi; Tim Self; Jeroen Stoof; Lee M Wheldon; Kristoffer Brännström; Raymond Wilson; Joanna Moreton; James W B Moir; Carina Sihlbom; Thomas Borén; Ann-Beth Jonsson; Panos Soultanas; Dlawer A A Ala'Aldeen

doi:10.1098/rsob.130048

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

Jafar Mahdavi, Pierre-Joseph Royer, Hong S Sjölinder, Sheyda Azimi, Tim Self, Jeroen Stoof, Lee M Wheldon, Kristoffer Brännström, Raymond Wilson, Joanna Moreton, James W B Moir, Carina Sihlbom, Thomas Borén, Ann-Beth Jonsson, Panos Soultanas, Dlawer A A Ala'Aldeen

Biology

Research output: Contribution to journal › Article › peer-review

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-α 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.

Original language	English
Pages (from-to)	130048
Journal	Open Biology
Volume	3
Issue number	10
DOIs	https://doi.org/10.1098/rsob.130048
Publication status	Published - Oct 2013

Keywords

Animals
Bacterial Proteins
Chromatin Immunoprecipitation
Cytokines
DNA-Binding Proteins
Disease Models, Animal
Fimbriae Proteins
Fimbriae, Bacterial
Gene Expression Regulation, Bacterial
Genome, Bacterial
Humans
Interleukin-8
Ligands
Meningitis, Bacterial
Mice
Mice, Transgenic
Neisseria meningitidis
Tumor Necrosis Factor-alpha
Virulence
Virulence Factors

Access to Document

10.1098/rsob.130048

Cite this

Mahdavi, J., Royer, P.-J., Sjölinder, H. S., Azimi, S., Self, T., Stoof, J., Wheldon, L. M., Brännström, K., Wilson, R., Moreton, J., Moir, J. W. B., Sihlbom, C., Borén, T., Jonsson, A.-B., Soultanas, P., & Ala'Aldeen, D. A. A. (2013). Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence. Open Biology, 3(10), 130048. https://doi.org/10.1098/rsob.130048

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title = "Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence",

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-α 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.",

keywords = "Animals, Bacterial Proteins, Chromatin Immunoprecipitation, Cytokines, DNA-Binding Proteins, Disease Models, Animal, Fimbriae Proteins, Fimbriae, Bacterial, Gene Expression Regulation, Bacterial, Genome, Bacterial, Humans, Interleukin-8, Ligands, Meningitis, Bacterial, Mice, Mice, Transgenic, Neisseria meningitidis, Tumor Necrosis Factor-alpha, Virulence, Virulence Factors",

author = "Jafar Mahdavi and Pierre-Joseph Royer and Sj{\"o}linder, {Hong S} and Sheyda Azimi and Tim Self and Jeroen Stoof and Wheldon, {Lee M} and Kristoffer Br{\"a}nnstr{\"o}m and Raymond Wilson and Joanna Moreton and Moir, {James W B} and Carina Sihlbom and Thomas Bor{\'e}n and Ann-Beth Jonsson and Panos Soultanas and Ala'Aldeen, {Dlawer A A}",

year = "2013",

month = oct,

doi = "10.1098/rsob.130048",

language = "English",

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pages = "130048",

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Mahdavi, J, Royer, P-J, Sjölinder, HS, Azimi, S, Self, T, Stoof, J, Wheldon, LM, Brännström, K, Wilson, R, Moreton, J, Moir, JWB, Sihlbom, C, Borén, T, Jonsson, A-B, Soultanas, P & Ala'Aldeen, DAA 2013, 'Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence', Open Biology, vol. 3, no. 10, pp. 130048. https://doi.org/10.1098/rsob.130048

TY - JOUR

T1 - Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence

AU - Mahdavi, Jafar

AU - Royer, Pierre-Joseph

AU - Sjölinder, Hong S

AU - Azimi, Sheyda

AU - Self, Tim

AU - Stoof, Jeroen

AU - Wheldon, Lee M

AU - Brännström, Kristoffer

AU - Wilson, Raymond

AU - Moreton, Joanna

AU - Moir, James W B

AU - Sihlbom, Carina

AU - Borén, Thomas

AU - Jonsson, Ann-Beth

AU - Soultanas, Panos

AU - Ala'Aldeen, Dlawer A A

PY - 2013/10

Y1 - 2013/10

N2 - 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-α 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.

AB - 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-α 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.

KW - Animals

KW - Bacterial Proteins

KW - Chromatin Immunoprecipitation

KW - Cytokines

KW - DNA-Binding Proteins

KW - Disease Models, Animal

KW - Fimbriae Proteins

KW - Fimbriae, Bacterial

KW - Gene Expression Regulation, Bacterial

KW - Genome, Bacterial

KW - Humans

KW - Interleukin-8

KW - Ligands

KW - Meningitis, Bacterial

KW - Mice

KW - Mice, Transgenic

KW - Neisseria meningitidis

KW - Tumor Necrosis Factor-alpha

KW - Virulence

KW - Virulence Factors

U2 - 10.1098/rsob.130048

DO - 10.1098/rsob.130048

M3 - Article

C2 - 24107297

SN - 2046-2441

VL - 3

SP - 130048

JO - Open Biology

JF - Open Biology

IS - 10

ER -