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Comparative Analysis of the Capacity of the Candida Species To Elicit Vaginal Immunopathology.
Infect Immun. 2018 12; 86(12)II

Abstract

The human fungal pathogen Candida albicans is the major etiological agent of vulvovaginal candidiasis (VVC). Despite this fact, other non-albicans Candida (NAC) species have frequently been reported, as well. Despite their presence in the vaginal environment, little is known about their capacities to elicit immune responses classically associated with C. albicans-mediated immunopathology, including neutrophil recruitment and proinflammatory cytokine signaling. Therefore, using a combination of in vitro and in vivo approaches, we undertook a comparative analysis to determine whether a representative panel of NAC species could colonize, induce immunopathological markers, or cause damage at the vaginal mucosa. Using a murine model of VVC, C. albicans was found to induce robust immunopathology (neutrophils and interleukin 1β [IL-1β]) and elicit mucosal damage. However, all the NAC species tested (including C. dubliniensis, C. tropicalis, C. parapsilosis, C. krusei, C. glabrata, and C. auris) induced significantly less damage and neutrophil recruitment than C. albicans, despite achieving similar early colonization levels. These results largely correlated with a notable lack of ability by the NAC species (including C. dubliniensis and C. tropicalis) to form hyphae both in vitro and in vivo Furthermore, both C. dubliniensis and C. tropicalis induced significantly less expression of the ECE1 gene encoding candidalysin, a key fungal virulence determinant driving VVC immunopathology. In order to determine the relative capacities of these species to elicit inflammasome-dependent IL-1β release, both wild-type and NLRP3[-/-] THP-1 cells were challenged in vitro While most species tested elicited only modest amounts of IL-1β, challenge with C. albicans led to significantly elevated levels that were largely NLRP3 dependent. Collectively, our findings demonstrate that although NAC species are increasingly reported as causative agents of VVC, C. albicans appears to be exceedingly vaginopathogenic, exhibiting robust immunopathology, hypha formation, and candidalysin expression. Thus, this study provides mechanistic insight into why C. albicans is overwhelmingly the major pathogen reported during VVC.

Authors+Show Affiliations

Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA brian.peters@uthsc.edu.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30249743

Citation

Willems, Hubertine M E., et al. "Comparative Analysis of the Capacity of the Candida Species to Elicit Vaginal Immunopathology." Infection and Immunity, vol. 86, no. 12, 2018.
Willems HME, Lowes DJ, Barker KS, et al. Comparative Analysis of the Capacity of the Candida Species To Elicit Vaginal Immunopathology. Infect Immun. 2018;86(12).
Willems, H. M. E., Lowes, D. J., Barker, K. S., Palmer, G. E., & Peters, B. M. (2018). Comparative Analysis of the Capacity of the Candida Species To Elicit Vaginal Immunopathology. Infection and Immunity, 86(12). https://doi.org/10.1128/IAI.00527-18
Willems HME, et al. Comparative Analysis of the Capacity of the Candida Species to Elicit Vaginal Immunopathology. Infect Immun. 2018;86(12) PubMed PMID: 30249743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative Analysis of the Capacity of the Candida Species To Elicit Vaginal Immunopathology. AU - Willems,Hubertine M E, AU - Lowes,David J, AU - Barker,Katherine S, AU - Palmer,Glen E, AU - Peters,Brian M, Y1 - 2018/11/20/ PY - 2018/07/06/received PY - 2018/09/12/accepted PY - 2018/9/27/pubmed PY - 2019/5/2/medline PY - 2018/9/26/entrez KW - Candida KW - NAC species KW - VVC KW - immunopathogenesis KW - inflammasome KW - vaginitis KW - vulvovaginal JF - Infection and immunity JO - Infect Immun VL - 86 IS - 12 N2 - The human fungal pathogen Candida albicans is the major etiological agent of vulvovaginal candidiasis (VVC). Despite this fact, other non-albicans Candida (NAC) species have frequently been reported, as well. Despite their presence in the vaginal environment, little is known about their capacities to elicit immune responses classically associated with C. albicans-mediated immunopathology, including neutrophil recruitment and proinflammatory cytokine signaling. Therefore, using a combination of in vitro and in vivo approaches, we undertook a comparative analysis to determine whether a representative panel of NAC species could colonize, induce immunopathological markers, or cause damage at the vaginal mucosa. Using a murine model of VVC, C. albicans was found to induce robust immunopathology (neutrophils and interleukin 1β [IL-1β]) and elicit mucosal damage. However, all the NAC species tested (including C. dubliniensis, C. tropicalis, C. parapsilosis, C. krusei, C. glabrata, and C. auris) induced significantly less damage and neutrophil recruitment than C. albicans, despite achieving similar early colonization levels. These results largely correlated with a notable lack of ability by the NAC species (including C. dubliniensis and C. tropicalis) to form hyphae both in vitro and in vivo Furthermore, both C. dubliniensis and C. tropicalis induced significantly less expression of the ECE1 gene encoding candidalysin, a key fungal virulence determinant driving VVC immunopathology. In order to determine the relative capacities of these species to elicit inflammasome-dependent IL-1β release, both wild-type and NLRP3[-/-] THP-1 cells were challenged in vitro While most species tested elicited only modest amounts of IL-1β, challenge with C. albicans led to significantly elevated levels that were largely NLRP3 dependent. Collectively, our findings demonstrate that although NAC species are increasingly reported as causative agents of VVC, C. albicans appears to be exceedingly vaginopathogenic, exhibiting robust immunopathology, hypha formation, and candidalysin expression. Thus, this study provides mechanistic insight into why C. albicans is overwhelmingly the major pathogen reported during VVC. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/30249743/Comparative_Analysis_of_the_Capacity_of_the_Candida_Species_To_Elicit_Vaginal_Immunopathology_ DB - PRIME DP - Unbound Medicine ER -