Analysis of Vaginal Cell Populations during Experimental Vaginal Candidiasis

Abstract

Studies with an estrogen-dependent murine model of vaginal candidiasis suggest that local cell-mediated immunity (CMI) is more important than systemic CMI for protection against vaginitis. The present study, however, showed that, compared to uninfected mice, little to no change in the percentage or types of vaginal T cells occurred during a primary vaginal infection or during a secondary vaginal infection where partial protection was observed. Furthermore, depletion of polymorphonuclear leukocytes (PMN) had no effect on infection in the presence or absence of pseudoestrus. These results indicate a lack of demonstrable effects by systemic CMI or PMN against vaginitis and suggest that if local T cells are important, they are functioning without showing significant increases in numbers within the vaginal mucosa during infection.

History and Update on Host Defense Against Vaginal Candidiasis

“…Studies in the animal model moved next to evaluation of local CMI, retaining the original hypothesis that T cells were important for protection against infection. Data emerged showing no appreciable change in resident T cells during infection, suggesting little if any protective role for local T cells, 33–35 despite evidence for a competent local CMI reported by us and others 36–38 in the absence of any organized lymphoid tissue found in other mucosal tissues (i.e. Peyer's patches in the gut, etc.…”

“…Interestingly, in one study, despite the lack of effect on fungal burden, neutropenia decreased inflammation (detected by microabcesses) associated with the infection 58 . Nevertheless, based on their vaginal presence at times in uninfected mice as well, 33,60 it appeared that PMNs may be present as a result of the normal menstrual cycle in mice rather than in response to infection 61 . Natural killer cells were also examined at the vaginal mucosa and found not to be present in naïve mice or during infection 62,63 .…”

“…Because of the lack of any demonstrable evidence for CMI or antibodies against primary RVVC, subsequent studies began to examine the role for innate resistance against Candida vaginitis. Several studies examined the role of polymorphonuclear neutrophils (PMNs) that were often inconsistently present in the vagina of infected mice 33,58,59 . The results were mixed; an early study showed increased susceptibility to infection in the absence of PMNs, 59 while later studies showed no effect of vaginal fungal burden when PMNs were depleted 33,58 .…”

“…Several studies examined the role of polymorphonuclear neutrophils (PMNs) that were often inconsistently present in the vagina of infected mice 33,58,59 . The results were mixed; an early study showed increased susceptibility to infection in the absence of PMNs, 59 while later studies showed no effect of vaginal fungal burden when PMNs were depleted 33,58 . Interestingly, in one study, despite the lack of effect on fungal burden, neutropenia decreased inflammation (detected by microabcesses) associated with the infection 58 .…”

Estrogen‐dependent induction of persistent vaginal candidosis in naïve mice

“…Vaginal T lymphocytes were isolated as previously described. [22][23][24][25] Briefly, vaginas of five to six mice per group per time-point were isolated, flushed with normal saline, opened up longitudinally, cut into 2 mm pieces and pooled. Tissue pieces were placed in 50 ml warm RPMI-1640 (Sigma Chemicals, St Louis, MO, USA) solution containing 10 mmol l )1 EDTA and 10 mmol l )1 dithiothreitol (DTT), tissue pieces were stirred for 30 min at 37°C.…”