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01.12.2014 | Original Investigation | Ausgabe 6/2014 Open Access

Medical Microbiology and Immunology 6/2014

Modulatory role of vitamin A on the Candida albicans-induced immune response in human monocytes

Zeitschrift:
Medical Microbiology and Immunology > Ausgabe 6/2014
Autoren:
Tilman E. Klassert, Anja Hanisch, Julia Bräuer, Esther Klaile, Kerstin A. Heyl, Michael M. Mansour, Jenny M. Tam, Jatin M. Vyas, Hortense Slevogt
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00430-014-0351-4) contains supplementary material, which is available to authorized users.
An erratum to this article can be found at http://​dx.​doi.​org/​10.​1007/​s00430-014-0362-1.

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.

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Zusatzmaterial
Suppl. Figure 1.- Dose-dependent regulation of the cytokine mRNA expression by retinoic acid. The modulatory effect of increasing concentrations of atRA (0.01 µM – 10 µM) on the C. albicans-induced cytokine expression was measured by qPCR. Shown is the percentage of inhibition as normalized to the C. albicans-induced mRNA expression of each gene. (TIFF 22,313 kb)
430_2014_351_MOESM1_ESM.tif
Suppl. Figure 2.- Modulatory role of atRA on the Dectin-1 expression in the absence of inflammatory stimuli. We measured the effect of atRA on the expression of Dectin-1 A) at transcriptional level after 5 h of incubation with 1 µM atRA by qPCR, and B) at the cell surface after 24 h of incubation by flow cytometry (data representative of 3 biological replicates). * p ≤ 0.05 (TIFF 67,138 kb)
430_2014_351_MOESM2_ESM.tif
Suppl. Figure 3.- Analysis of the expression of Dectin-1, TLR2 and Galectin-3 after 4 h of incubation with C. albicans (in the presence or absence of 1 µM atRA). Receptor expression was measured on protein level by flow cytometry for A) Dectin-1 and B) TLR2, and by Western Blot for C) Galectin-3 after 4 h of incubation. Incipient regulation of the Dectin-1 expression is observed after C. albicans challenge, being potentiated in the presence of atRA. The data are representative of 3 independent experiments. (TIFF 59,077 kb)
430_2014_351_MOESM3_ESM.tif
Suppl. Figure 4.- Regulation of the cytokine mRNA expression by retinoic acid exposure over different time-periods. Monocytes were pre-incubated with 1 µM atRA for either 0,5 or 24 h. Then the cells were challenged with C. albicans for 5 h and the cytokine expression was measured by Real-Time qPCR. Shown is the percentage of inhibition achieved by atRA pre-incubation on the C. albicans-induced cytokine expression. (TIFF 27,642 kb)
430_2014_351_MOESM4_ESM.tif
Literatur
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