Pathogenesis analysis of vulvovaginal candidiasis in a mouse model using oligonucleotide microarrays.

Abstract

：Objective To investigatethe pathogenesis of vulvovaginal candidiasis.Methods Thirty mice were randomly and equallydivided into 3 groups,i.e.,infected group treated with estrogen and innoculated with aclinical isolate of C. albicans,negative centrel group treated with estrogen andinoculated with physiological saline.blank control group without any treatment.All micewere kilied on day 7 after inoculation,vaginal tissue samples were obtained and subjectedto pathological examination and staining.Total RNA was extracted from these samples aswell as Candida isolates and reference strains,and hybridized with self-designedoligonucleotide chips.Then,signal value of vulvovaginal candidiasis-associated factors wascompared between infected group and blank control group,and a 2-fold difference wasconsidered as significant.Results Compared with the blank centrol group,the geneexpression of 39 factors increased while that of 4 factors decreased in the infeetedgroup.In the case of host immunity,the expression of inflammatory chemokines generallyinereased,and that of regulatory factors of adaptive immunity,including interleukin(IL)-1,IL-4,IL-6,IL-10,IL-12,tumor necrosis factor(TNF)-α,nuclear factor (NF)-κB andtransforming growth factor (TGF)-β Was also enhanced todifferent degrees.TLR4,a humoral component of innate immune response,increased in allspecimens from infected group,whereas Toll-like receptor(TLR)2 expression increased onlyin one third of these speciraens.The expression of virulent factors including EFG1 (amodulatory factor of hyphal formation),secreted aspartic proteinase(SAP)2,SAP4,SAP5,SAP6,SAP10,lipase(LIP)2,LIP4 and HWP(a major cell wall protein)1increased in pathogenic strains.Among these differentially expressed genes,monocytechemoattractant protein(MCP)-1,macrophage inflammatory protein(MIP)-1α,MIP-2,IL-1,TLR4,LIP4 andHWP1,which were involved in extracellular hydrolysis,hyphal formation,phenotypic switchingand host native immunity,were increased significantly in all specimens from the infectedgroup.Conclusions Both the deficiency of adaptive immunity and increased virulence ofpathogen strains are involved in the pathogenesis of vulvovaginal candidiasis,and TLR4possibly plays an important role in local immunity of hosts with vulvovaginal candidiasis. Key words: Oligonucleotide array sequenceanalysis; Candidiasis; vulvovaginal; Disease models; animal; Cytokines; Virulence factors