Cell-wall deficient L. monocytogenes L-forms feature abrogated pathogenicity.

Area of Science:

• Microbiology
• Immunology
• Bacterial Pathogenesis

Background:

• Stable L-forms are cell wall-deficient bacteria capable of indefinite propagation.
• The pathogenicity and immune response triggered by L-forms of intracellular pathogens remain incompletely understood.

Purpose of the Study:

• To investigate the pathogenicity of Listeria monocytogenes L-forms.
• To determine if L-forms can trigger an innate immune response.

Main Methods:

• Phagocytosis assays using L. monocytogenes L-forms with macrophages (non-activated, IFN-γ preactivated, and bone marrow-derived).
• Assessment of bacterial persistence and elimination within phagocytes.
• Analysis of virulence factor expression and host immune response (IFN-β, cytokine response in MyD88-deficient dendritic cells).

Main Results:

• L. monocytogenes L-forms exhibited persistence in non-activated macrophages but were effectively eliminated by activated macrophages.
• Down-regulation of virulence factors was observed in L-forms.
• L-forms did not trigger Interferon-β (IFN-β), indicating impaired phagosomal escape.
• Host response was TLR-dependent, with abrogated cytokine production in MyD88-deficient dendritic cells.

Conclusions:

• Listeria monocytogenes L-forms display significantly attenuated pathogenicity.
• Diminished virulence factor expression and reduced innate immune recognition contribute to this attenuation.
• L-form bacteria are ultimately eliminated from host phagocytes.