title: Differential Effects of Vitamins A and D on the Transcriptional Landscape of Human Monocytes during Infection.
abstract: Vitamin A and vitamin D are essential nutrients with a wide range of pleiotropic effects in humans. Beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. Nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of immune processes. In the present study, we performed a comprehensive RNA-seq-based approach to define the whole immunomodulatory role of vitamins A and D during infection. Using human monocytes as host cells, we characterized the differential role of both vitamins upon infection with three different pathogens: Aspergillus fumigatus, Candida albicans and Escherichia coli. Both vitamins showed an unexpected ability to counteract the pathogen-induced transcriptional responses. Upon infection, we identified 346 and 176 immune-relevant genes that were regulated by atRA and vitD, respectively. This immunomodulatory activity was dependent on the inflammatory stimulus, allowing us to distinguish regulatory patterns which were specific for each stimulatory setting. Moreover, we explored possible direct and indirect mechanisms of vitamin-mediated regulation of the immune response. Our findings highlight the importance of vitamin-monitoring in critically ill patients. Moreover, our results underpin the potential of atRA and vitD as therapeutic options for anti-inflammatory treatment.
authors.affiliation: Jena University Hospital, Septomics Research Center, Jena, 07745, Germany.
authors.forename: Tilman E
authors.initials: TE
authors.lastname: Klassert
authors.affiliation: Jena University Hospital, Septomics Research Center, Jena, 07745, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bräuer
authors.affiliation: Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hölzer
authors.affiliation: Jena University Hospital, Septomics Research Center, Jena, 07745, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stock
authors.affiliation: Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Riege
authors.affiliation: Jena University Hospital, Septomics Research Center, Jena, 07745, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zubiría-Barrera
authors.affiliation: Jena University Hospital, Septomics Research Center, Jena, 07745, Germany.|Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, Jena, 07747, Germany.
authors.forename: Mario M
authors.initials: MM
authors.lastname: Müller
authors.affiliation: Jena University Hospital, Institute of Transfusion Medicine, Jena, 07747, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Rummler
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Department of Infection Biology, Jena, 07745, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
authors.affiliation: Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Marz
authors.affiliation: Jena University Hospital, Septomics Research Center, Jena, 07745, Germany.
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
mesh_terms: D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors; D056747:Immunomodulation / Q000187:drug effects; D007239:Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D059467:Transcriptome; D014801:Vitamin A / Q000494:pharmacology*; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D007155:Immunologic Factors; D014801:Vitamin A; D014807:Vitamin D