title: Lactobacillus crispatusModulates Vaginal Epithelial Cell Innate Response toCandida albicans.
abstract: BACKGROUND
  Vulvovaginal candidiasis is caused by Candida albicans. The vaginal epithelium, as the first site of the initial stage of infection by pathogens, plays an important role in resisting genital tract infections. Moreover, lactobacilli are predominant members of the vaginal microbiota that help to maintain a normal vaginal microenvironment. Therefore, Lactobacillus crispatus was explored for its capacity to intervene in the immune response of vaginal epithelial cells VK2/E6E7 to C. albicans.
  
  
  METHODS
  We examined the interleukin-2 (IL-2), 4, 6, 8, and 17 produced by VK2/E6E7 cells infected with C. albicans and treated with L. crispatus in vitro. The capacity of L. crispatus to adhere to VK2/E6E7 and inhibit C. albicans growth was also tested by scanning electron microscopy (SEM) and adhesion experiments.
  
  
  RESULTS
  Compared with group VK2/E6E7 with C. albicans, when treated with L. crispatus, the adhesion of C. albicans to VK2/E6E7 cells decreased significantly by 52.87 ± 1.22%, 47.03 ± 1.35%, and 42.20 ± 1.55% under competition, exclusion, and displacement conditions, respectively. SEM revealed that the invasion of C. albicans into VK2/E6E7 cells was caused by induced endocytosis and active penetration. L. crispatus could effectively protect the cells from the virulence of hyphae and spores of C. albicans and enhance the local immune function of the VK2/E6E7 cells. The concentrations of IL-2, 6, and 17 were upregulated significantly (P < 0.01) and that of IL-8 were downregulated significantly (P < 0.01) in infected VK2/E6E7 cells treated with L. crispatus. The concentration of IL-4 was similar to that of the group VK2/E6E7 with C. albicans (24.10 ± 0.97 vs. 23.12 ± 0.76 pg/ml, P = 0.221).
  
  
  CONCLUSIONS
  L. crispatus can attenuate the virulence of C. albicans, modulate the secretion of cytokines and chemokines, and enhance the immune response of VK2/E6E7 cells in vitro. The vaginal mucosa has a potential function in the local immune responses against pathogens that can be promoted by L. crispatus.
authors.affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Niu
authors.affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing 100034, China.
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Liu
mesh_terms: D002176:Candida albicans / Q000472:pathogenicity*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D000070003:Lactobacillus crispatus / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D014621:Vagina / Q000166:cytology*
chemical_list: D020381:Interleukin-17; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D015847:Interleukin-4