Advertisement

Different Host Immunological Response to C. albicans by Human Oral and Vaginal Epithelial Cells

  • Ying Gao
  • Guanzhao Liang
  • Qiong Wang
  • Xiaodong She
  • Dongmei Shi
  • Yongnian Shen
  • Xiaohong Su
  • Xiang Wang
  • Wenmei Wang
  • Dongmei Li
  • Weida LiuEmail author
Original Paper
  • 58 Downloads

Abstract

Objective

The immunological mechanisms behind different mucosa against candidiasis are largely unknown. In this study, we investigate the natural protective mechanisms and local cytokine responses of C. albicans-infected oral and vaginal epithelial cells.

Method

The cell lines (Leuk-1 and VK2/E6E7) were cultured with C. albicans (SC5314, Δals3, and Δssa1) in indicated ratio, respectively. The morphological changes and colony growth of C. albicans were observed to evaluate the fungicidal ability of epithelial cells, and the cellular morphological changes and LDH activity measurements were used to assess cell damage. Further, we assess the production of cytokines and chemokines in co-culture supernatants using enzyme-linked immunosorbent assay (ELISA).

Result

Our results show that the oral and vaginal epithelial cells use different strategies to combat this pathogen. Infected oral epithelial cells are adept at the production of cytokines (GM-CSF, IL-1α, and IL-1β) and chemokines (IL-8, MIP-3α, and RANTES), and yet, vaginal cells are more proficient at direct fungal killing. However, both epithelial cells play only a minor role in adaptive immunity to C. albicans. Further, C. albicans Als3p and Ssa1p genes also participate in local immune response since deletion of ALS3 or SSA1 causes reduction in cytokine and chemokine levels in both oral and vaginal cells. The dramatic decreases in both fungal % of cytotoxicity and the secretion of such cytokines as GM-CSF, MIP-3α, and RANTES in Δssa1-infected oral cells were consistent with a delayed germination process in that mutant.

Conclusion

Human oral and vaginal epithelial cells performed different host response to C. albicans by fungal killing ability or secreting cytokines and chemokines.

Keywords

Candida albicans Cytokines Oral epithelial cells Vaginal epithelial cells 

Notes

Acknowledgement

This work was supported by National Key Basic Research Program of China (2013CB531605), National Natural Science Foundation of China (No. 81071332), and Jiangsu Provincial Special Program of Medical Science (BL2012003). We thank Professor Li Mao for providing Leuk-1 cell line, Dr. Raina Fichorova for kindly providing cell lines VK2/E6E7, and Dr. Scott G Filler for kindly gift of mutant strains shown in this study. We also would like to thank Professor Wantao Chen for his kind help to our experiment.

References

  1. 1.
    Calderone RA. Candida and candidiasis. Washington, DC: ASM Press; 2002.Google Scholar
  2. 2.
    Sobel JD. Vulvovaginal candidiasis. Lancet. 2007;369:1961–71.CrossRefGoogle Scholar
  3. 3.
    Cenci E, Mencacci A, Spaccapelo R, Tonnetti L, Mosci P, Enssle KH, et al. T helper cell type 1 (Th1)- and Th2-like responses are present in mice with gastric candidiasis but protective immunity is associated with Th1 development. J Infect Dis. 1995;171:1279–88.CrossRefGoogle Scholar
  4. 4.
    Fidel PL Jr, Lynch ME, Redondo-Lopez V, Sobel JD, Robinson R. Systemic cell-mediated immune reactivity in women with recurrent vulvovaginal candidiasis. J Infect Dis. 1993;168:1458–65.CrossRefGoogle Scholar
  5. 5.
    Fidel PL Jr, Cutright J, Steele C. Effects of reproductive hormones on experimental vaginal candidiasis. Infect Immun. 2000;68:651–7.CrossRefGoogle Scholar
  6. 6.
    Steele C, Leigh J, Swoboda R, Fidel PL Jr. Growth inhibition of Candida by human oral epithelial cells. J Infect Dis. 2000;182:1479–85.CrossRefGoogle Scholar
  7. 7.
    Barousse MM, Steele C, Dunlap K, Espinosa T, Boikov D, Sobel JD, et al. Growth inhibition of Candida albicans by human vaginal epithelial cells. J Infect Dis. 2001;184:1489–93.CrossRefGoogle Scholar
  8. 8.
    Moyes DL, Runglall M, Murciano C, Shen C, Nayar D, Thavaraj S, et al. A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host Microbe. 2010;8:225–35.CrossRefGoogle Scholar
  9. 9.
    Moyes DL, Murciano C, Runglall M, Islam A, Thavaraj S, Naglik JR. Candida albicans yeast and hyphae are discriminated by MAPK signaling in vaginal epithelial cells. PLoS ONE. 2011;6:e26580.CrossRefGoogle Scholar
  10. 10.
    Murciano C, Moyes DL, Runglall M, Tobouti P, Islam A, Hoyer LL, et al. Evaluation of the role of Candida albicans agglutinin-like sequence (Als) proteins in human oral epithelial cell interactions. PLoS ONE. 2012;7:e33362.CrossRefGoogle Scholar
  11. 11.
    Yang W, Yan L, Wu C, Zhao X, Tang J. Fungal invasion of epithelial cells. Microbiol Res. 2014;169:803–10.CrossRefGoogle Scholar
  12. 12.
    Sun JN, Solis NV, Phan QT, Bajwa JS, Kashleva H, Thompson A, et al. Host cell invasion and virulence mediated by Candida albicans Ssa1. PLoS Pathog. 2010;6:e1001181.CrossRefGoogle Scholar
  13. 13.
    Kumamoto CA. Niche-specific gene expression during C. albicans infection. Curr Opin Microbiol. 2008;11:325–30.CrossRefGoogle Scholar
  14. 14.
    de Koning HD, Rodijk-Olthuis D, van Vlijmen-Willems IM, Joosten LA, Netea MG, Schalkwijk J, et al. A comprehensive analysis of pattern recognition receptors in normal and inflamed human epidermis: upregulation of dectin-1 in psoriasis. J Invest Dermatol. 2010;130:2611–20.CrossRefGoogle Scholar
  15. 15.
    Weindl G, Naglik JR, Kaesler S, Biedermann T, Hube B, Korting HC, et al. Human epithelial cells establish direct antifungal defense through TLR4-mediated signaling. J Clin Invest. 2007;117:3664–72.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Wang WM, Ye P, Qian YJ, Gao YF, Li JJ, Sun FF, et al. Effects of whole cigarette smoke on human beta defensins expression and secretion by oral mucosal epithelial cells. Tob Induc Dis. 2015;13:3.CrossRefGoogle Scholar
  17. 17.
    Anukam KC, Reid G. In vitro evaluation of the viability of vaginal cells (VK2/E6E7) and probiotic Lactobacillus species in lemon juice. Sex Health. 2009;6:67–74.CrossRefGoogle Scholar
  18. 18.
    Wachtler B, Wilson D, Haedicke K, Dalle F, Hube B. From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells. PLoS ONE. 2011;6:e17046.CrossRefGoogle Scholar
  19. 19.
    Dongari-Bagtzoglou A, Fidel PL Jr. The host cytokine responses and protective immunity in oropharyngeal candidiasis. J Dent Res. 2005;84:966–77.CrossRefGoogle Scholar
  20. 20.
    Steele C, Fidel PL Jr. Cytokine and chemokine production by human oral and vaginal epithelial cells in response to Candida albicans. Infect Immun. 2002;70:577–83.CrossRefGoogle Scholar
  21. 21.
    Carmi Y, Voronov E, Dotan S, Lahat N, Rahat MA, Fogel M, et al. The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol. 2009;183:4705–14.CrossRefGoogle Scholar
  22. 22.
    Apte RN, Voronov E. Is interleukin-1 a good or bad ‘guy’ in tumor immunobiology and immunotherapy? Immunol Rev. 2008;222:222–41.CrossRefGoogle Scholar
  23. 23.
    Rider P, Carmi Y, Guttman O, Braiman A, Cohen I, Voronov E, et al. IL-1alpha and IL-1beta recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol. 2011;187:4835–43.CrossRefGoogle Scholar
  24. 24.
    Cohen I, Rider P, Carmi Y, Braiman A, Dotan S, White MR, et al. Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc Natl Acad Sci U S A. 2010;107:2574–9.CrossRefGoogle Scholar
  25. 25.
    Godaly G, Bergsten G, Hang L, Fischer H, Frendeus B, Lundstedt AC, et al. Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection. J Leukoc Biol. 2001;69:899–906.PubMedGoogle Scholar
  26. 26.
    Homey B, Dieu-Nosjean MC, Wiesenborn A, Massacrier C, Pin JJ, Oldham E, et al. Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis. J Immunol. 2000;164:6621–32.CrossRefGoogle Scholar
  27. 27.
    Luster AD. Chemokines–chemotactic cytokines that mediate inflammation. N Engl J Med. 1998;338:436–45.CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Ying Gao
    • 1
  • Guanzhao Liang
    • 1
  • Qiong Wang
    • 1
  • Xiaodong She
    • 1
  • Dongmei Shi
    • 1
    • 2
  • Yongnian Shen
    • 1
  • Xiaohong Su
    • 3
  • Xiang Wang
    • 4
  • Wenmei Wang
    • 4
  • Dongmei Li
    • 1
    • 5
  • Weida Liu
    • 1
    Email author
  1. 1.Department of Mycology, Institute of DermatologyChinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Jiangsu Key Laboratory of Molecular Biology for Skin Disease and STIsNanjingChina
  2. 2.Department of DermatologyJiningChina
  3. 3.STD Clinic, Institute of DermatologyChinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)NanjingChina
  4. 4.Department of Oral Medicine, Nanjing Stomatological HospitalMedical School of Nanjing UniversityNanjingChina
  5. 5.Department of Microbiology & ImmunologyGeorgetown University Medical CenterWashingtonUSA

Personalised recommendations