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

• Published in: Open biology Vol. 3; no. 10; p. 130048
• Main Authors: Mahdavi, Jafar, Royer, Pierre-Joseph, Sjölinder, Hong S., Azimi, Sheyda, Self, Tim, Stoof, Jeroen, Wheldon, Lee M., Brännström, Kristoffer, Wilson, Raymond, Moreton, Joanna, Moir, James W. B., Sihlbom, Carina, Borén, Thomas, Jonsson, Ann-Beth, Soultanas, Panos, Ala'Aldeen, Dlawer A. A.
• Format: Journal Article
• Language: English
• Published: England The Royal Society 2013
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological Sciences; Biologiska vetenskaper; Chromatin Immunoprecipitation; Cytokines; Cytokines - metabolism; Disease Models, Animal; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fimbriae Proteins - genetics; Fimbriae Proteins - metabolism; Fimbriae, Bacterial - genetics; Fimbriae, Bacterial - metabolism; Gene Expression Regulation, Bacterial; Genome, Bacterial; Glycosylation; Humans; Interleukin-8 - metabolism; Ligands; Meningitis, Bacterial - metabolism; Meningitis, Bacterial - microbiology; Mice; Mice, Transgenic; Neisseria meningitidis; Neisseria meningitidis - genetics; Neisseria meningitidis - metabolism; Neisseria meningitidis - pathogenicity; Patho-Adaptation; Transcriptional Regulators; Tumor Necrosis Factor-alpha - metabolism; Type Iv Pili; Virulence; Virulence Factors - genetics; Virulence Factors - metabolism; glycosylation; transcriptional regulators; Neisseria meningitidis; cytokines; patho-adaptation; type IV pili
• ISSN: 2046-2441; 2046-2441
• DOI: 10.1098/rsob.130048

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.