Joan Hui Juan Lim, Sharada Ravikumar, Yan-Ming Wang, Thomas Paulraj Thamboo, Lizhen Ong, Jinmiao Chen, Jessamine Geraldine Goh, Sen Hee Tay, Lufei Chengchen, Mar Soe Win, Winnie Leong, Titus Lau, Roger Foo, Haris Mirza, Kevin Shyong Wei Tan, Sunil Sethi, Ai Leng Khoo, Wee Joo Chng, Motomi Osato, Mihai G. Netea, Yue Wang, and Louis Yi Ann Chai Bimodal Influence of Vitamin D in Host Response to Systemic Candida Infection—Vitamin D Dose Matters J Infect Dis. (2015) 212 (4): 635-644 first published online January 22, 2015 doi:10.1093/infdis/jiv033
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.
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