Key findings, in chronological order, from studies reported between 1990 and 2017 investigating the pathogenesis of VVC/RVVC

Lack of adaptive immunity in protectionLocal rather than systemic immunity is critical for host defense against infection
Immunoregulatory mechanisms are responsible for the lack of adaptive immunity in the vagina
Innate resistance by epithelial cellsEpithelial cell anti-Candida activity via annexin A1 is predominant innate protective response
Immunopathology by PMNsParadigm change: innate responses by neutrophils rather than adaptive immune deficiency contribute to immunopathogenesis
S100 alarmins and IL-1β produced by epithelial cells in response to Candida via TLR4 and SIGNR1 and involving the NLRP3 inflammasome are key to initiation of the immunopathogenic response associated with symptomatic infection
Morphogenesis by C. albicans is required for the immunopathological response
Candidalysin is predominant molecule invoking epithelial cell damage leading to the epithelial cell activation and subsequent immunopathogenic response
Mechanism of immunopathogenic response uncovered: heparan sulfate in the vaginal environment serves as a competitive inhibitor of neutrophil-Candida interaction required for killing, resulting in a state of neutrophil anergy