Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice

Rana, Minakshi; Bella, Andrea La; Lederman, Rivka; Volpe, Bruce T.; Sherry, Barbara; Diamond, Betty

doi:10.1172/jci146776

Cited by 9 publications

(24 citation statements)

References 60 publications

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“…In addition to Tfh cells, follicular DCs are also involved in the functional regulation of FO B cells. A recent study has shown that the impairment of antigen-specific FO B cell humoral responses in CLP mice may be due to follicular DCs dysfunction rather than due to primarily intrinsic defects in the B-cell compartment ( Rana et al, 2021 ).…”

Section: The Key Role Of B Cells In Sepsismentioning

confidence: 99%

The emerging roles and therapeutic potential of B cells in sepsis

Liu

Yang

et al. 2022

Front. Pharmacol.

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Sepsis is a life-threatening syndrome caused by anomalous host response to infection. The pathogenesis of sepsis is complex, and immune dysfunction is the central link in its occurrence and development. The sepsis immune response is not a local and transient process but a complex and continuous process involving all major cell types of innate and adaptive immunity. B cells are traditionally studied for their ability to produce antibodies in the context of mediating humoral immunity. However, over the past few years, B cells have been increasingly recognized as key modulators of adaptive and innate immunity, and they can participate in immune responses by presenting antigens, producing cytokines, and modulating other immune cells. Recently, increasing evidence links B-cell dysfunction to mechanisms of immune derangement in sepsis, which has drawn attention to the powerful properties of this unique immune cell type in sepsis. Here, we reviewed the dynamic alterations of B cells and their novel roles in animal models and patients with sepsis, and provided new perspectives for therapeutic strategies targeting B cells in sepsis.

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Section: The Key Role Of B Cells In Sepsismentioning

confidence: 99%

The emerging roles and therapeutic potential of B cells in sepsis

Liu

Yang

et al. 2022

Front. Pharmacol.

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“…First, sepsis is shown to have a dysregulated immune response highlighted by the upregulation of the expression level of TLR4 (36)(37)(38). Immunological dysregulation is considered as a critical cause of sepsis (39,40). However, most studies investigated individual genes at a high-throughput level involving DEGs, followed by enrichment pathway analysis (4,41,42).…”

Section: Discussionmentioning

confidence: 99%

LPIN1 Is a Regulatory Factor Associated With Immune Response and Inflammation in Sepsis

et al. 2022

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ObjectivesSepsis is a clinical disease that is typically treated in the intensive care unit, and the complex pathophysiology under this disease has not been thoroughly understood. While ferroptosis is involved in inflammation and infection, its effect in sepsis is still unknown. The study aimed to identify ferroptosis-related genes in sepsis, providing translational potential therapeutic targets.MethodsThe dataset GSE65682 was used to download the sample source from the Gene Expression Omnibus (GEO) database. Consensus weighted gene co-expression network analysis (WGCNA) was performed to find suspected modules of sepsis. The differentially expressed genes (DEGs) most significantly associated with mortality were intersected with those altered by lipopolysaccharide (LPS) treatment and were further analyzed for the identification of main pathways of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The related pathway markers were further verified by qPCR.ResultsA total of 802 blood samples with sepsis were included for WGCNA, which identified 21 modules. Intersected with ferroptosis databases and LPS treatment groups, we identified two ferroptosis-related genes: PEBP1 and LPIN1. Only LPIN1 contributes to a poor outcome. Then, 205 DEGs were further identified according to the high or low LPIN1 expression. Among them, we constructed a gene regulatory network with several transcriptional factors using the NetworkAnalyst online tool and identified that these genes mostly correlate with inflammation and immune response. The immune infiltration analysis showed that lower expression of LPIN1 was related to macrophage infiltration and could be an independent predictor factor of the survival status in sepsis patients. Meanwhile, the multivariate Cox analysis showed that LPIN1 had a significant correlation with survival that was further verified by in vitro and in vivo experiments.ConclusionIn conclusion, LPIN1 could become a reliable biomarker for patient survival in sepsis, which is associated with immune and inflammation status.

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“…In contrast, neutralising TNF during Ehrlichia muris infection enhances GC responses 21 but we observed an enhanced loss of FDCs and no GC response during STm-infection. The loss of FDCs, GCs and impaired humoral immunity after interference with the TNF signalling using either TNF-neutralising antibodies or gene-targeted mice has been described extensively in steady-state conditions 36,46,47,53,54 and under inflammatory environments such as sepsis 55 . These results suggest that during active infection, the targeting of specific cell types may be more difficult than targeting soluble factors such as TNF and highlights the potential difficulty in using single agent interventions to target different bacterial infections as each infection may have a distinct immune signature.…”

Section: Previous Studies Have Shown How Non-b Cell-intrinsic Mechani...mentioning

confidence: 99%

Salmonellainfection induces the reorganisation of follicular dendritic cell networks concomitant with the failure to generate germinal centres

Marcial‐Juárez

Pérez-Toledo

Nayar

et al. 2022

Preprint

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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.

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Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice

Cited by 9 publications

References 60 publications

The emerging roles and therapeutic potential of B cells in sepsis

The emerging roles and therapeutic potential of B cells in sepsis

LPIN1 Is a Regulatory Factor Associated With Immune Response and Inflammation in Sepsis

Salmonellainfection induces the reorganisation of follicular dendritic cell networks concomitant with the failure to generate germinal centres

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