title: Modulatory role of vitamin A on the Candida albicans-induced immune response in human monocytes.
abstract: Beyond its well-documented role in reproduction, embryogenesis and maintenance of body tissues, vitamin A has attracted considerable attention due to its immunomodulatory effects on both the innate and the adaptive immune responses. In infectious diseases, vitamin A has been shown to have a host-protective effect in infections of bacterial, viral or protozoan origin. Nevertheless, its impact in fungal infections remains unknown. Meanwhile, the frequency of invasive mycoses keeps on growing, with Candida albicans being the major opportunistic fungal pathogen and associated with high mortality. In the present work, we explored the impact of all-trans retinoic acid (atRA), the most active metabolite of vitamin A, on the innate immune response against C. albicans in human monocytes. Our results show a strong immunomodulatory role for atRA, leading to a significant down-regulation of the fungi-induced expression and secretion of the pro-inflammatory cytokines TNFα, IL6 and IL12. Moreover, atRA significantly suppressed the expression of Dectin-1, a major fungal pattern recognition receptor, as well as the Dectin-1-dependent cytokine production. Both RAR-dependent and RAR-independent mechanisms seem to play a role in the atRA-mediated immunomodulation. Our findings open a new direction to elucidate the role of vitamin A on the immune function during fungal infections.
authors.affiliation: Septomics Research Center, Jena University Hospital, Albert-Einstein-Strasse 10, 07745, Jena, Germany.
authors.forename: Tilman E
authors.initials: TE
authors.lastname: Klassert
authors.forename: Anja
authors.initials: A
authors.lastname: Hanisch
authors.forename: Julia
authors.initials: J
authors.lastname: Bräuer
authors.forename: Esther
authors.initials: E
authors.lastname: Klaile
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: Heyl
authors.forename: Michael K
authors.initials: MK
authors.lastname: Mansour
authors.forename: Michael M
authors.initials: MM
authors.lastname: Mansour
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Tam
authors.forename: Jatin M
authors.initials: JM
authors.lastname: Vyas
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D037181:Lectins, C-Type / Q000032:analysis; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D014801:Vitamin A / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D037181:Lectins, C-Type; D014801:Vitamin A; C546929:CLEC7A protein, human; D000099181:Dectin-1