Publication date: Dec 30, 2024
Antibody-mediated protection against pathogens is crucial to a healthy life. However, the recent SARS-CoV-2 pandemic has shown that pre-existing comorbid conditions including kidney disease account for compromised humoral immunity to infections. Individuals with kidney disease are not only susceptible to infections but also exhibit poor vaccine-induced antibody response. Using multiple mouse models of kidney disease, we demonstrate that renal dysfunction inhibits germinal center (GC) response against T-dependent antigens. GC B cells exhibit increased apoptosis in kidney disease. Uremic toxin hippuric acid drives loss of mitochondrial membrane potential, leading to increased apoptosis of GC B cells in a G-protein-coupled receptor 109A dependent manner. Finally, GC B cells and antibody titer are diminished in mice with kidney disease following influenza virus infection, a major cause of mortality in individuals with renal disorders. These results provide a mechanistic understanding of how renal dysfunction suppresses humoral immunity in patients with kidney disease.
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Semantics
Type | Source | Name |
---|---|---|
disease | MESH | kidney disease |
disease | MESH | infections |
pathway | REACTOME | Apoptosis |
disease | IDO | toxin |
disease | MESH | influenza |
disease | MESH | virus infection |
disease | MESH | comorbidity |
disease | IDO | infection |
drug | DRUGBANK | Pentaerythritol tetranitrate |
disease | IDO | immune response |
disease | MESH | Uremia |
pathway | REACTOME | Immune System |
disease | IDO | process |
disease | MESH | infectious disease |
pathway | REACTOME | Infectious disease |
disease | MESH | complications |
pathway | REACTOME | Influenza Infection |
disease | MESH | defects |
disease | MESH | chemically induced |
disease | MESH | fibrosis |
drug | DRUGBANK | Nitrogen |
disease | IDO | assay |
disease | IDO | production |
disease | IDO | blood |
drug | DRUGBANK | Proline |
drug | DRUGBANK | Coenzyme M |
drug | DRUGBANK | Aspartame |
drug | DRUGBANK | Monomethyl fumarate |
drug | DRUGBANK | Methylergometrine |
disease | IDO | cell |
disease | MESH | COVID-19 |
disease | MESH | Disease Models Animal |
disease | MESH | Orthomyxoviridae Infections |