Bimodal Influence of Vitamin D in Host Response to Systemic Candida Infection-Vitamin D Dose Matters

J Infect Dis. 2015 Aug 15;212(4):635-44. doi: 10.1093/infdis/jiv033. Epub 2015 Jan 22.


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.

Keywords: 1,25(OH)2D3; cytokine; interferon gamma; suppressor of cytokine signaling (SOCS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candidiasis / drug therapy*
  • Candidiasis / immunology
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / pharmacology*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear
  • Mice
  • Mice, Inbred BALB C
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Vitamin D / blood*


  • RNA, Messenger
  • STAT Transcription Factors
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Vitamin D
  • Cholecalciferol
  • Interferon-gamma