Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions.
Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses.
Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute), Jena, Germany.|Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
Betty
B
Hebecker
Department of General, Visceral and Vascular Surgery, Experimental Transplantation Surgery, Jena University Hospital, Jena, Germany.|Research Group Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute), Jena, Germany.|Department of Bioinformatics, Friedrich-Schiller-University Jena, Germany.
Sebastian
S
Vlaic
Research Group Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute), Jena, Germany.
Theresia
T
Conrad
Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.|Department of Anaesthesiology and Intensive Care Therapy, Jena University Hospital, Jena, Germany.
Michael
M
Bauer
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute), Jena, Germany.
Sascha
S
Brunke
Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute), Jena, Germany.
Mario
M
Kapitan
Research Group Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute), Jena, Germany.
Jörg
J
Linde
Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.|Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute), Jena, Germany.|Friedrich-Schiller-University, Jena, Germany.
Bernhard
B
Hube
Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knöll Institute), Jena, Germany.|Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.|Friedrich-Schiller-University, Jena, Germany.
Ilse D
ID
Jacobsen
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D002175:Candida / Q000502:physiology; D002177:Candidiasis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D002473:Cell Wall / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D054884:Host-Pathogen Interactions / Q000235:genetics*; D025301:Hyphae / Q000235:genetics; D007109:Immunity / Q000235:genetics; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity / Q000235:genetics*; D010587:Phagocytosis; D025341:Principal Component Analysis; D013045:Species Specificity; D015854:Up-Regulation / Q000235:genetics
D007501:Iron