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

Area of Science:

• Microbiology
• Immunology
• Pathogen-host interactions

Background:

• Commensal pathogens can cause disease by switching to a virulent state, but the mechanisms are unclear.
• Neisseria meningitidis, a cause of meningitis, can increase virulence.
• Understanding pathogen state switching is crucial for disease control.

Purpose of the Study:

• To investigate the mechanisms by which Neisseria meningitidis modulates gene expression and virulence.
• To identify host factors and bacterial components involved in the switch to virulence.
• To elucidate the role of type IV pili in pathogen-host interactions.

Main Methods:

• Investigated Neisseria meningitidis gene expression modulation via host cytokine uptake.
• Utilized type IV pili (Tfp) and PilT ATPase activity in uptake studies.
• Identified Tfp subunits PilE and PilQ as ligands for TNF-α and IL-8.
• Performed glycan-dependent binding assays.
• Assessed virulence in a mouse model following deletion of Tfp subunits.

Main Results:

• Neisseria meningitidis imports pro-inflammatory cytokines (TNF-α, IL-8) via type IV pili.
• PilT ATPase activity is essential for this cytokine uptake.
• PilE and PilQ subunits bind cytokines in a glycan-dependent manner.
• Deletion of PilE and PilQ reduced virulence and increased mouse survival.

Conclusions:

• A novel mechanism of pathogen virulence modulation is proposed, involving Tfp-mediated sensing and import of host cytokines.
• Pathogens utilize twitching motility of Tfp to sense and import host elicitors, facilitating adaptation to inflamed environments.
• This switching mechanism contributes to disease development in Neisseria meningitidis infections.