TY - UNPB
T1 - Salmonella infection induces the reorganisation of follicular dendritic cell networks concomitant with the failure to generate germinal centres
AU - Marcial-Juárez, Edith
AU - Perez-Toledo, Marisol
AU - Nayar, Saba
AU - Pipi, Elena
AU - Alshayea, Areej
AU - Persaud, Ruby
AU - Jossi, Sian E.
AU - Lamerton, Rachel
AU - Barone, Francesca
AU - Henderson, Ian R.
AU - Cunningham, Adam F.
PY - 2022/12/12
Y1 - 2022/12/12
N2 - Germinal centres (GCs) are sites where plasma and memory B cells form to generate high-affinity, Ig class switched antibodies. Specialised stromal cells called follicular dendritic cells (FDCs) are essential for GC formation. During systemic Salmonella Typhimurium (STm) infection GCs are absent, whereas extensive extrafollicular switched antibody responses are maintained. The mechanisms that underpin the absence of GC formation are incompletely understood. Here, we show that STm-induces a reversible disruption of niches within the splenic microenvironment, including the T and B cell compartments and the marginal zone. Alongside to these effects post-infection, mature FDC networks are strikingly absent, whereas immature FDC precursors, including marginal sinus pre-FDCs (MadCAM-1+) and perivascular Pre-FDCs (PDGFRβ+) are enriched. As normal FDC networks re-establish, extensive GCs become detectable throughout the spleen. Therefore, the reorganisation of FDC networks and the loss of GC responses are key, parallel features of systemic STm infections.
AB - Germinal centres (GCs) are sites where plasma and memory B cells form to generate high-affinity, Ig class switched antibodies. Specialised stromal cells called follicular dendritic cells (FDCs) are essential for GC formation. During systemic Salmonella Typhimurium (STm) infection GCs are absent, whereas extensive extrafollicular switched antibody responses are maintained. The mechanisms that underpin the absence of GC formation are incompletely understood. Here, we show that STm-induces a reversible disruption of niches within the splenic microenvironment, including the T and B cell compartments and the marginal zone. Alongside to these effects post-infection, mature FDC networks are strikingly absent, whereas immature FDC precursors, including marginal sinus pre-FDCs (MadCAM-1+) and perivascular Pre-FDCs (PDGFRβ+) are enriched. As normal FDC networks re-establish, extensive GCs become detectable throughout the spleen. Therefore, the reorganisation of FDC networks and the loss of GC responses are key, parallel features of systemic STm infections.
U2 - 10.1101/2022.12.11.519997
DO - 10.1101/2022.12.11.519997
M3 - Preprint
BT - Salmonella infection induces the reorganisation of follicular dendritic cell networks concomitant with the failure to generate germinal centres
PB - bioRxiv
ER -