title: Vitamin D deficiency causes defective resistance to Aspergillus fumigatus in mice via aggravated and sustained inflammation.
abstract: BACKGROUND
  Vitamin D plays an important role in pulmonary resistance and immunity, and its deficiency has been linked to various respiratory infections. Little is known about the effect of vitamin D deficiency on host pulmonary defense to Aspergillus fumigatus (A. fumigatus).
  
  
  METHODS
  Mice raised on vitamin D sufficient or deficient diets were infected intratracheally with A. fumigatus conidia. Mortality, fungal growth, weight loss and lung histology were monitored. Alveolar macrophages (AMs) were stimulated with A. fumigatus conidia in vitro. The kinetics of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), chemokines (CXCL1, CCL3), and pattern recognition receptors (Toll-like receptor [TLR] 2, TLR 4 and dectin-1) expression in the lungs and AMs were measured.
  
  
  RESULTS
  Upon A. fumigatus infection, vitamin D deficient mice showed higher mortality, greater fungal load, and more weight loss than its sufficient counterparts. Vitamin D deficient mice demonstrated aggravated and prolonged histological evidence of lung inflammation as well as enhanced BAL cell counts, dominated by neutrophils after A. fumigatus inoculation. Increased basal levels of pro-inflammatory cytokines in the lungs and AMs from naïve vitamin D deficient mice were observed. Upon A. fumigatus exposure, vitamin D deficiency led to enhanced and sustained expression of TNF-α, IL-1β, IL-6, CXCL1 and CCL3 both in vivo and in vitro. Up-regulation of TLR2, TLR4 and dectin-1was observed in the lungs and AMs from vitamin D deficient mice both at baseline and after A. fumigatus exposure.
  
  
  CONCLUSIONS
  Vitamin D deficiency causes defective pulmonary resistance to A. fumigatus in mice, possibly by the enhanced basal expression of pattern recognition receptors and pro-inflammatory cytokines, which induced excessive inflammatory response in response to A. fumigatus challenge.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Ehong
authors.initials: E
authors.lastname: Cao
authors.affiliation: Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Wanchun
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Clinical Microbiology, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Clinical Microbiology, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Lining
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D054405:Chemokine CCL3 / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000150:complications* / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D054405:Chemokine CCL3; D054360:Chemokine CXCL1; D037181:Lectins, C-Type; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000099181:Dectin-1