Salmonella infection induces the reorganization of follicular dendritic cell networks concomitant with the failure to generate germinal centers

Edith Marcial-Juárez; Marisol Pérez-Toledo; Saba Nayar; Elena Pipi; Areej Alshayea; Ruby Persaud; Sian E Jossi; Rachel Lamerton; Francesca Barone; Ian R Henderson; Adam F Cunningham

doi:10.1016/j.isci.2023.106310

Salmonella infection induces the reorganization of follicular dendritic cell networks concomitant with the failure to generate germinal centers

iScience. 2023 Mar 2;26(4):106310. doi: 10.1016/j.isci.2023.106310. eCollection 2023 Apr 21.

Authors

Affiliations

¹ Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, United Kingdom.
² Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, West Midlands, B15 2TT, United Kingdom.
³ National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, UK and Sandwell and West Birmingham Trust, Birmingham, West Midlands, B15 2TH, United Kingdom.
⁴ Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD4072, Australia.

Abstract

Germinal centers (GCs) are sites where plasma and memory B cells form to generate high-affinity, Ig class-switched antibodies. Specialized stromal cells called follicular dendritic cells (FDCs) are essential for GC formation. During systemic Salmonella Typhimurium (STm) infection GCs are absent, whereas extensive extrafollicular and switched antibody responses are maintained. The mechanisms that underpin the absence of GC formation are incompletely understood. Here, we demonstrate that STm induces a reversible disruption of niches within the splenic microenvironment, including the T and B cell compartments and the marginal zone. Alongside these effects after 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 reorganization of FDC networks and the loss of GC responses are key, parallel features of systemic STm infections.

Keywords: Cell biology; Components of the immune system; Immune response; Immunology; Microbiology.

Abstract

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