Abstract:

Objective To investigate the pathogenesis of vulvovaginal candidiasis. Methods Thirty mice were randomly and equally divided into 3 groups, i.e., infected group treated with estrogen and innoculated with a clinical isolate of C. albicans, negative control group treated with estrogen and inoculated with physiological saline, blank control group without any treatment. All mice were killed on day 7 after inoculation, vaginal tissue samples were obtained and subjected to pathological examination and staining. Total RNA was extracted from these samples as well as Candida isolates and reference strains, and hybridized with self-designed oligonucleotide chips. Then, signal value of vulvovaginal candidiasis-associated factors was compared between infected group and blank control group, and a 2-fold difference was considered as significant. Results Compared with the blank control group, the gene expression of 39 factors increased while that of 4 factors decreased in the infected group. In the case of host immunity, the expression of inflammatory chemokines generally increased, 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 and transforming growth factor （TGF）-β was also enhanced to different degrees. TLR4, a humoral component of innate immune response, increased in all specimens from infected group, whereas Toll-like receptor （TLR） 2 expression increased only in one third of these specimens. The expression of virulent factors including EFG1 （a modulatory factor of hyphal formation）, secreted aspartic proteinase （SAP） 2, SAP4, SAP5, SAP6, SAP10, lipase （LIP） 2, LIP4 and HWP （a major cell wall protein） 1 increased in pathogenic strains. Among these differentially expressed genes, monocyte chemoattractant protein （MCP）-1, macrophage inflammatory protein （MIP）-1α, MIP-2, IL-1, TLR4, LIP4 and HWP1, which were involved in extracellular hydrolysis, hyphal formation, phenotypic switching and host native immunity, were increased significantly in all specimens from the infected group. Conclusions Both the deficiency of adaptive immunity and increased virulence of pathogen strains are involved in the pathogenesis of vulvovaginal candidiasis, and TLR4 possibly plays an important role in local immunity of hosts with vulvovaginal candidiasis.