cholecalciferol and Candidiasis

The incidence of intra-abdominal candidiasis (IAC), characterized by high morbidity and mortality, has become a serious concern. The limitations of current antifungal drugs on the market underscores the importance of the development of novel antifungal agents. In the present study, the antifungal activity of vitamin D

Topics: Animals; Antifungal Agents; Candida; Candida albicans; Candidiasis; Carbon; Cholecalciferol; Coenzymes; Cytokines; Interferons; Mice; Microbial Sensitivity Tests; Tumor Necrosis Factors

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS). We described that Candida albicans (Ca) aggravates experimental autoimmune encephalomyelitis (EAE) that is a model to study MS. We also observed that vaccination with a myelin peptide (MOG) in the presence of vitamin D (VitD) protected mice against EAE. In this work, we investigated whether Ca infection interferes with the efficacy of this vaccine.. EAE was induced in C57BL/6 female mice previously vaccinated with MOG+VitD and then infected 3 days before encephalomyelitis induction.. Vaccination was able to control EAE development in infected mice. These animals gained weight, and only a few progressed to very low clinical scores. Protection was confirmed by a lower inflammatory infiltration in the CNS and was also associated with a reduced production of encephalitogenic cytokines by spleen and CNS cell cultures. The elevated percentage of CD25(+) FoxP3(+) cells suggests that regulatory T cells are involved in the protection. Adoptive transfer of splenocytes from mice vaccinated with MOG+VitD supports the view that protection is mediated by immunoregulatory cells.. Together, these experiments provide evidence demonstrating that EAE can be prevented by the inverse vaccination with MOG+VitD even in the presence of a disease-aggravating infectious agent.

Topics: Animals; Body Weight; Candida albicans; Candidiasis; Cells, Cultured; Central Nervous System; Cholecalciferol; Cytokines; Dendritic Cells; Disease Models, Animal; Down-Regulation; Encephalomyelitis, Autoimmune, Experimental; Female; Forkhead Transcription Factors; Indoleamine-Pyrrole 2,3,-Dioxygenase; Lymph Nodes; Mice; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; Vitamins

Vitamin D level is linked to susceptibility to infections, but its relevance in candidemia is unknown. We aimed to investigate the in vivo sequelae of vitamin D3 supplementation in systemic Candida infection. Implicating the role of vitamin D in Candida infections, we showed that candidemic patients had significantly lower 25-OHD concentrations. Candida-infected mice treated with low-dose 1,25(OH)2D3 had reduced fungal burden and better survival relative to untreated mice. Conversely, higher 1,25(OH)2D3 doses led to poor outcomes. Mechanistically, low-dose 1,25(OH)2D3 induced proinflammatory immune responses. This was mediated through suppression of SOCS3 and induction of vitamin D receptor binding with the vitamin D-response elements in the promoter of the gene encoding interferon γ. These beneficial effects were negated with higher vitamin D3 doses. While the antiinflammatory effects of vitamin D3 are well described, we found that, conversely, lower doses conferred proinflammatory benefits in Candida infection. Our study highlights caution against extreme deviations of vitamin D levels during infections.

Topics: Animals; Candidiasis; Cholecalciferol; Cohort Studies; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Inflammation; Interferon-gamma; Leukocytes, Mononuclear; Mice; Mice, Inbred BALB C; Promoter Regions, Genetic; RNA, Messenger; STAT Transcription Factors; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Vitamin D