Intracellular antibody neutralizes Listeria growth

Area of Science:

• Immunology
• Microbiology
• Bacterial Pathogenesis

Background:

• Listeria monocytogenes is an intracellular bacterium requiring robust host immune responses for clearance.
• Listeriolysin O (LLO) is a key virulence factor enabling Listeria escape from phagosomes into the host cell cytoplasm.
• Antibody-based therapies are explored for infectious diseases, but mechanisms within host cells are not fully understood.

Purpose of the Study:

• To investigate the impact of a neutralizing anti-LLO monoclonal antibody (mAb) on macrophage-mediated Listeria resistance.
• To elucidate the mechanism by which anti-LLO mAb influences intracellular bacterial handling and growth.
• To determine if anti-LLO mAb confers protection independently of known macrophage effector functions.

Main Methods:

• Infection of primary macrophages with Listeria monocytogenes in the presence of anti-LLO mAb.
• Quantification of intracellular bacterial growth and localization (phagosome vs. cytosol).
• Assessment of antibody-dependent cellular functions, including Fcgamma receptor engagement, IFNgamma signaling, and reactive oxygen/nitrogen species production.

Main Results:

• Anti-LLO mAb significantly reduced intracellular Listeria growth within macrophages.
• The antibody blocked the translocation of Listeria from the phagosome to the cytosol, a process dependent on LLO.
• Protection mediated by anti-LLO mAb was independent of Fcgamma receptor expression, IFNgamma signaling, and nitric oxide/superoxide production.

Conclusions:

• Neutralizing antibodies against LLO can effectively control intracellular bacterial growth within macrophages.
• Anti-LLO mAb acts intracellularly to neutralize LLO, preventing bacterial escape into the cytosol.
• This study reveals a novel antibody-mediated mechanism for controlling intracellular bacterial infections, independent of classical immune activation pathways.