Bacterial infection disrupts established germinal center reactions through monocyte recruitment and impaired...

Area of Science:

• Immunology
• Microbiology
• Pathogen Interactions

Background:

• Consecutive pathogen exposures are common and can modify host immunity.
• The impact of secondary bacterial infections on ongoing adaptive immune responses is not well understood.

Purpose of the Study:

• To investigate how a secondary bacterial infection affects adaptive immune responses, specifically germinal center (GC) reactions.

Main Methods:

• Salmonella Typhimurium (STm) infection model.
• Analysis of germinal center reactions in lymphoid organs.
• Monocyte recruitment studies (CCR2-dependent).
• Assessment of cellular respiration, TNFα, and IFNγ.
• Experiments with influenza, Plasmodium, commensals, LPS vaccination, and Listeria monocytogenes.

Main Results:

• STm infection recruited Sca-1+ monocytes into lymphoid organs, disrupting pre-existing GC reactions.
• GC responses to influenza, Plasmodium, or commensals were impaired by STm infection.
• GC collapse was mediated by CCR2-dependent monocyte recruitment, not direct B cell interaction.
• Impaired cellular respiration and dependence on TNFα and IFNγ were observed.
• Monocyte recruitment and GC disruption occurred with LPS vaccination and Listeria infection.

Conclusions:

• Systemic innate immune activation during severe bacterial infection compromises antibody-mediated immunity.
• Sca-1+ monocyte recruitment is a key mechanism disrupting GC responses.
• IFNγ is crucial for Sca-1+ monocyte differentiation and subsequent GC disruption.