Intestinal colonization by Candida albicans alters inflammatory responses in Bruton's tyrosine kinase-deficient mice
Autor: | Strijbis, Karin, Yilmaz, Omer H, Dougan, Stephanie K, Esteban, Alexandre, Gröne, Andrea, Kumamoto, Carol A, Ploegh, Hidde L, Strategic Infection Biology, PB SIB, LS Infectiebiologie (Bacteriologie), I&I SIB2, LS Pathologie, Sub Cellular Protein Chemistry |
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Přispěvatelé: | Strategic Infection Biology, PB SIB, LS Infectiebiologie (Bacteriologie), I&I SIB2, LS Pathologie, Sub Cellular Protein Chemistry |
Rok vydání: | 2014 |
Předmět: |
medicine.medical_treatment
Pathology and Laboratory Medicine Biochemistry Immune Receptors immune system diseases Transforming Growth Factor beta Animal Cells hemic and lymphatic diseases Candida albicans Agammaglobulinaemia Tyrosine Kinase Medicine and Health Sciences Intestinal Mucosa Immune Response Mice Knockout Fungal Pathogens Gastrointestinal tract Multidisciplinary Immune System Proteins biology Dextran Sulfate Interleukin-17 Candidiasis Fungal Diseases Organ Size Protein-Tyrosine Kinases Colitis Immunohistochemistry Corpus albicans Interleukin-10 Intestines medicine.anatomical_structure Cytokine Infectious Diseases Medical Microbiology Host-Pathogen Interactions Medicine Cytokines Inflammation Mediators Cellular Types Pathogens Research Article Colon Science Immune Cells Immunology Spleen Immunopathology Gastroenterology and Hepatology Opportunistic Infections Microbiology medicine Bruton's tyrosine kinase Animals Humans Microbial Pathogens Macrophages Soft Tissue Infections Inflammatory Bowel Disease Wild type Immunity Biology and Life Sciences Proteins Cell Biology biology.organism_classification medicine.disease digestive system diseases Yeast Infections biology.protein Clinical Immunology Pattern Recognition Receptors |
Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 11, p e112472 (2014) PLoS One, 9(11). Public Library of Science |
ISSN: | 1932-6203 |
Popis: | The commensal yeast Candida albicans is part of the human intestinal microflora and is considered a "pathobiont", a resident microbe with pathogenic potential yet harmless under normal conditions. The aim of this study was to investigate the effect of C. albicans on inflammation of the intestinal tract and the role of Bruton's tyrosine kinase (Btk). Btk is an enzyme that modulates downstream signaling of multiple receptors involved in innate and adaptive immunity, including the major anti-fungal receptor Dectin-1. Colitis was induced in wild type and Btk-/- mice by treatment with dextran sodium sulfate (DSS) and the gastrointestinal tract of selected treatment groups were then colonized with C. albicans. Colonization by C. albicans neither dampened nor exacerbated inflammation in wild type mice, but colon length and spleen weight were improved in Btk-deficient mice colonized with C. albicans. Neutrophil infiltration was comparable between wild type and Btk-/- mice, but the knockout mice displayed severely reduced numbers of macrophages in the colon during both DSS and DSS/Candida treatment. Smaller numbers and reduced responsiveness of Btk-/- macrophages might partially explain the improved colon length of Btk-/- mice as a result of Candida colonization. Surprisingly, DSS/Candida-treated Btk-/- animals had higher levels of certain pro-inflammatory cytokines and levels of the anti-inflammatory cytokine TGF-β were reduced compared to wild type. A clustering and correlation analysis showed that for wild type animals, spleen TGF-β and colon IL-10 and for Btk-/- spleen and colon levels of IL-17A best correlated with the inflammatory parameters. We conclude that in Btk-/- immunocompromised animals, colonization of the gastrointestinal tract by the commensal yeast C. albicans alters inflammatory symptoms associated with colitis. |
Databáze: | OpenAIRE |
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