title: Massive Effect on LncRNAs in Human Monocytes During Fungal and Bacterial Infections and in Response to Vitamins A and D.
abstract: Mycoses induced by C.albicans or A.fumigatus can cause important host damage either by deficient or exaggerated immune response. Regulation of chemokine and cytokine signaling plays a crucial role for an adequate inflammation, which can be modulated by vitamins A and D. Non-coding RNAs (ncRNAs) as transcription factors or cis-acting antisense RNAs are known to be involved in gene regulation. However, the processes during fungal infections and treatment with vitamins in terms of therapeutic impact are unknown. We show that in monocytes both vitamins regulate ncRNAs involved in amino acid metabolism and immune system processes using comprehensive RNA-Seq analyses. Compared to protein-coding genes, fungi and bacteria induced an expression change in relatively few ncRNAs, but with massive fold changes of up to 4000. We defined the landscape of long-ncRNAs (lncRNAs) in response to pathogens and observed variation in the isoforms composition for several lncRNA following infection and vitamin treatment. Most of the involved antisense RNAs are regulated and positively correlated with their sense protein-coding genes. We investigated lncRNAs with stimulus specific immunomodulatory activity as potential marker genes: LINC00595, SBF2-AS1 (A.fumigatus) and RP11-588G21.2, RP11-394l13.1 (C.albicans) might be detectable in the early phase of infection and serve as therapeutic targets in the future.
authors.affiliation: Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Riege
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: Tilman E
authors.initials: TE
authors.lastname: Klassert
authors.affiliation: Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.|FLI Leibniz Institute for Age Research, 07745 Jena, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Barth
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.|Institute of Virology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Collatz
authors.affiliation: Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.|Chair of Bioinformatics, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Hufsky
authors.affiliation: Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.|Institute of Virology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Nelly
authors.initials: N
authors.lastname: Mostajo
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.|Institute of Virology, Philipps-University Marburg, 35043 Marburg, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Vogel
authors.affiliation: Jena University Hospital, Septomics Research Center, Jena, 07745, Germany.
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
authors.affiliation: Friedrich Schiller University, Bioinformatics/High Throughput Analysis, Jena, 07743, Germany.|FLI Leibniz Institute for Age Research, 07745 Jena, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Marz
mesh_terms: D001424:Bacterial Infections / Q000235:genetics* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D009181:Mycoses / Q000235:genetics* / Q000382:microbiology; D016372:RNA, Antisense / Q000235:genetics; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D014801:Vitamin A / Q000378:metabolism / Q000494:pharmacology*; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014801:Vitamin A; D014807:Vitamin D