Impaired neutrophil extracellular trap-forming capacity contributes to susceptibility to chronic vaginitis in a mouse model of vulvovaginal candidiasis

Authors

Junko Yano, LSU Health Sciences Center - New OrleansFollow
Paul L. Fidel, LSU Health Sciences Center - New OrleansFollow

Document Type

Article

Publication Date

1-30-2024

Publication Title

Infection and Immunity

Abstract

Vulvovaginal candidiasis (VVC), caused by is characterized by aberrant inflammation by polymorphonuclear neutrophils (PMNs) in the vaginal lumen. Data from the established murine model shows that despite potent antifungal properties, PMNs fail to clear due to local heparan sulfate that inhibits the interaction between PMNs and , resulting in chronic vaginal immunopathology. To understand the role of neutrophil extracellular traps (NETs) in defense against at the vaginal mucosa, we investigated the NET-forming capacity of PMNs in chronic VVC-susceptible (CVVC-S/C3H) and -resistant (CVVC-R/CD-1) mouse strains. Immunofluorescence revealed the formation of NETs (release of DNA with PMN-derived antimicrobial proteins) in PMN cocultures using vaginal conditioned medium (VCM) generated from CVVC-R/CD-1 mice, similar to NET-inducing positive controls. Under these NETotic conditions, PMNs released high levels of double-stranded DNA bound with NET-associated proteins, concomitant with substantial killing activity. In contrast, PMN cocultures in VCM from CVVC-S/C3H mice lacked NET formation together with reduced antifungal activity. Similar results were observed : active NET interaction followed by fungal clearance in inoculated CVVC-R/CD-1 mice, and sustained high vaginal fungal burden and no evidence of NETs in inoculated CVVC-S/C3H mice. Furthermore, the level of Ki67 expression, a putative NETotic PMN marker, was significantly reduced in vaginal lavage fluid from CVVC-S/C3H mice compared to CVVC-R/CD-1 mice. Finally, scanning electron microscopy revealed that PMNs in CVVC-R, but not CVVC-S, conditions exhibited NETs in direct contact with hyphae and . These results suggest that VVC-associated immunopathology includes impaired NET-mediated antifungal activity.

First Page

e0035023

PubMed ID

38289125

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Yano, Junko and Fidel, Paul L., "Impaired neutrophil extracellular trap-forming capacity contributes to susceptibility to chronic vaginitis in a mouse model of vulvovaginal candidiasis" (2024). School of Dentistry Faculty Publications. 117.
https://digitalscholar.lsuhsc.edu/sod_facpubs/117