Germinal centre B cell disruption by non-typhoidal Salmonella

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Salmonella enterica serovar Typhimurium (STm) causes invasive non-typhoidal salmonellosis (iNTS), a severe health issue in sub-Saharan Africa.
• STm infection leads to germinal center (GC) disruption, impairing adaptive immune responses.
• Current understanding of bacteria-host interactions driving GC collapse is incomplete.

Purpose of the Study:

• To investigate the impact of STm on germinal center integrity and B cell responses.
• To explore the mechanisms by which STm disrupts GC reactions.
• To inform the development of novel vaccine strategies against iNTS.

Main Methods:

• Utilized an iNTS-like mouse model to study STm infection.
• Analyzed germinal center reactions and B cell populations post-infection.
• Investigated the roles of lipopolysaccharide (LPS) and type 3 secretion effectors.

Main Results:

• STm significantly disrupts germinal center formation and maintenance.
• Impaired formation of high-affinity, long-lived antibody-producing B cells and memory B cells.
• STm also induces an extrafollicular B cell response, but antibody longevity is uncertain.

Conclusions:

• Germinal center integrity is a critical factor in effective immunity against STm.
• Vaccine strategies for iNTS should aim to protect GC integrity.
• GC parameters should be included as endpoints in preclinical iNTS vaccine trials.