Clinical and Immunological Insights into Oral Candidiasis
Candida Biofilms and Host Cytokine Responses, Koya-Iraq
DOI:
https://doi.org/10.14500/aro.12632Keywords:
Biofilm, Candida albicans, Interleukin-17, Neutrophils, Oral CandidiasisAbstract
Oral candidiasis (OC) is a widespread opportunistic fungal disease primarily caused by Candida albicans, with non-albicans Candida species progressively recognized as new pathogens. Previous studies have typically focused on a single microbial feature, such as the frequency of Candida species or biofilm formation, or on host immune responses, including cytokine activity, but have rarely investigated both simultaneously. These gaps have limited understanding of how fungal virulence factors interact with host immunity and have hindered the identification of reliable disease biomarkers. The present investigation examined the prevalence, species distribution, biofilm activity, and host immune responses in OC participants in Kurdistan, Iraq. A total of 154 suspected cases were directly cultured on Sabouraud Dextrose Agar and HiCrome™ Candida Differential agar and analyzed with the VITEK 2 system. Among them, 61 participants (39.6%) tested positive for OC, with C. albicans as the predominant isolate (59.4%), followed by Candida kefyr, Candida dubliniensis, Candida parapsilosis, Candida tropicalis, and Candida krusei. More than half of the isolates produced biofilm, and C. tropicalis exhibited the strongest biofilm-forming capacity. Immunological profiling revealed significantly higher neutrophil counts and elevated serum interleukin (IL)-10 and IL-17 in OC-positive participants. Diabetes mellitus appeared as the most common comorbidity. By integrating Candida species characterization with host immune profiling, this research provides new insights into the interaction between host defense mechanisms and fungal pathogenicity. In contrast to earlier work, the current analysis directly related species-specific biofilm capacity with neutrophil and cytokine dynamics, establishing IL-17 as a potential biomarker of OC activity.
Downloads
References
AL-JAFAR, H. 2016. Provisional study of Kuwait adult hematology reference range. J Hematol Thromb, 2, 4.
ALRAYYES, S. F., ALRUWAILI, H. M., TAHER, I. A., ELRAHAWY, K. M., ALMAEEN, A. H., ASHEKHI, A. O. & ALAM, M. K. 2019. Oral Candidal carriage and associated risk indicators among adults in Sakaka, Saudi Arabia. BMC Oral Health, 19, 86.
AMRAN, S. S. D., SYAIDA, A. A. R., JALIL, M. T. M., NOR, N. H. M. & YAHYA, M. 2024. Preparation of biofilm assay using 96-well and 6-well microplates for quantitative measurement and structural characterization: a review. Sci Lett, 18, 121-34.
BASNET, A., TAMANG, B., SHRESTHA, M. R., SHRESTHA, L. B., RAI, J. R., MAHARJAN, R., DAHAL, S., SHRESTHA, P. & RAI, S. K. 2023. Assessment of four in vitro phenotypic biofilm detection methods in relation to antimicrobial resistance in aerobic clinical bacterial isolates. PLoS One, 18, e0294646.
BUTASSI, E., SVETAZ, L., CARPINELLA, M. C., EFFERTH, T. & ZACCHINO, S. 2021. Fungal biofilms as a valuable target for the discovery of natural products that cope with the resistance of medically important fungi—Latest findings. Antibiotics, 10, 1053.
CHEN, H., ZHOU, X., REN, B. & CHENG, L. 2020. The regulation of hyphae growth in Candida albicans. Virulence, 11, 337-348.
CHIMENZ, R., TROPEANO, A., CHIRICO, V., CERAVOLO, G., SALPIETRO, C. & CUPPARI, C. 2022. IL‐17 serum level in patients with chronic mucocutaneous candidiasis disease. Pediatric Allergy and Immunology, 33, 77-79.
CHO, E., PARK, Y., KIM, K.-Y., HAN, D., KIM, H. S., KWON, J.-S. & AHN, H.-J. 2021. Clinical characteristics and relevance of oral Candida biofilm in tongue smears. Journal of Fungi, 7, 77.
CONTI, H. R. & GAFFEN, S. L. 2015. IL-17–Mediated immunity to the opportunistic fungal pathogen Candida albicans. The Journal of Immunology, 195, 780-788.
DA SILVA, C. 2021. Development and implementation of laboratory methodologies to study microbial multicellular communities. Universidade do Minho (Portugal).
FURTUNA, D. K., DEBORA, K., WARSITO, E. B. & SOETRISNO, S. 2018. Comparison of microbiological examination by test tube and Congo red agar methods to detect biofilm production on clinical isolates. Folia Medica Indonesiana, 54, 22-28.
FURUE, M., FURUE, K., TSUJI, G. & NAKAHARA, T. 2020. Interleukin-17A and keratinocytes in psoriasis. International journal of molecular sciences, 21, 1275.
GAFFEN, S. L. & MOUTSOPOULOS, N. M. 2020. Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity. Science immunology, 5, eaau4594.
GAZENDAM, R. P., VAN HAMME, J. L., TOOL, A. T., HOOGENBOEZEM, M., VAN DEN BERG, J. M., PRINS, J. M., VITKOV, L., VAN DE VEERDONK, F. L., VAN DEN BERG, T. K. & ROOS, D. 2016. Human neutrophils use different mechanisms to kill Aspergillus fumigatus conidia and hyphae: evidence from phagocyte defects. The Journal of immunology, 196, 1272-1283.
HALIMI, A., MORTAZAVI, N., MEMARIAN, A., ZAHEDI, M., NIKNEJAD, F., SOHRABI, A. & SARRAF, S. J. 2022. The relation between serum levels of interleukin 10 and interferon-gamma with oral candidiasis in type 2 diabetes mellitus patients. BMC Endocrine Disorders, 22, 296.
HELLSTEIN, J. W. & MAREK, C. L. 2019. Candidiasis: red and white manifestations in the oral cavity. Head and neck Pathology, 13, 25-32.
HWANG, S. Y., LIM, Y. K., CHOE, K. W., CHOI, Y. H. & LEE, M.-K. 2024. Seasonality and epidemiological trends in species distribution and antifungal susceptibility of Candida species isolated from various clinical specimens conducted during 2011–2022, Korea: a retrospective surveillance study. Annals of Clinical Microbiology, 27, 185-196.
JAN, A., BASHIR, G., ALTAF, I., FOMDA, B. A., HAMID, S. & JAN, K. 2022. Evaluation of various phenotypic methods for differentiation of Candida dubliniensis from Candida albicans. Journal of Microbiological Methods, 193, 106400.
JIANG, L., FANG, M., TAO, R., YONG, X. & WU, T. 2020. Recombinant human interleukin 17A enhances the anti‐Candida effect of human oral mucosal epithelial cells by inhibiting Candida albicans growth and inducing antimicrobial peptides secretion. Journal of Oral Pathology & Medicine, 49, 320-327.
KAYONGO, A., ROBERTSON, N. M., SIDDHARTHAN, T., NTAYI, M. L., NDAWULA, J. C., SANDE, O. J., BAGAYA, B. S., KIRENGA, B., MAYANJA-KIZZA, H. & JOLOBA, M. L. 2023. Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease. Frontiers in immunology, 13, 1085551.
KITAYA, S., KANAMORI, H., KATORI, Y. & TOKUDA, K. 2023. Clinical features and outcomes of persistent candidemia caused by Candida albicans versus non-albicans Candida species: a focus on antifungal resistance and follow-up blood cultures. Microorganisms, 11, 928.
MALINOVSKÁ, Z., ČONKOVÁ, E. & VÁCZI, P. 2023. Biofilm formation in medically important Candida species. Journal of Fungi, 9, 955.
MBA, I. E. & NWEZE, E. I. 2020. Mechanism of Candida pathogenesis: revisiting the vital drivers. European Journal of Clinical Microbiology & Infectious Diseases, 39, 1797-1819.
MEHTA, R. & WYAWAHARE, A. S. 2016. Evaluation of hicrome Candida differential agar for species identification of Candida isolates from various clinical samples. Int J Cont Med Res, 3, 1219-1222.
MELHEM, M., BERTOLETTI, A., LUCCA, H., SILVA, R., MENEGHIN, F. & SZESZS, M. 2013. Use of the VITEK 2 system to identify and test the antifungal susceptibility of clinically relevant yeast species. Brazilian Journal of Microbiology, 44, 1257-1266.
NOVIANTI, Y. & SUFIAWATI, I. 2023. Clinical assessment and management in improving the quality of life of HIV/AIDS patients with oral candidiasis: a case series. HIV/AIDS-Research and Palliative Care, 683-696.
NUNCÃ, A.-M., COCULESCU, E. C. & COCULESCU, B.-I. 2022. The Role of General Factors in the Pathogenesis of Oral Candidiasis. Romanian Archives of Microbiology and Immunology, 81, 271-277.
PAVLOVA, A. & SHARAFUTDINOV, I. 2020. Recognition of Candida albicans and role of innate type 17 immunity in oral candidiasis. Microorganisms, 8, 1340.
PEREIRA, R., DOS SANTOS FONTENELLE, R. O., DE BRITO, E. & DE MORAIS, S. 2021. Biofilm of Candida albicans: formation, regulation and resistance. Journal of applied microbiology, 131, 11-22.
POKHREL, S., BOONMEE, N., TULYAPRAWAT, O., PHARKJAKSU, S., THAIPISUTIKUL, I., CHAIRATANA, P., NGAMSKULRUNGROJ, P. & MITRPANT, C. 2022. Assessment of biofilm formation by Candida albicans strains isolated from hemocultures and their role in pathogenesis in the zebrafish model. Journal of Fungi, 8, 1014.
RAMOS, L. S., MELLO, T. P., BRANQUINHA, M. H. & SANTOS, A. L. 2020. Biofilm formed by Candida haemulonii species complex: Structural analysis and extracellular matrix composition. Journal of Fungi, 6, 46.
RODRIGUES, M. E., GOMES, F. & RODRIGUES, C. F. 2019. Candida spp./bacteria mixed biofilms. Journal of Fungi, 6, 5.
SHARMA, P., SAMBYAL, S., SHRIVASTAVA, D. & NADIFI, S. 2017. Phenotypic detection of biofilms in Candida species isolated from various clinical specimen. Int J Adv Res, 5, 10.21474.
SHEN, H., YU, Y., CHEN, S.-M., SUN, J.-J., FANG, W., GUO, S.-Y., HOU, W.-T., QIU, X.-R., ZHANG, Y. & CHEN, Y.-L. 2020. Dectin-1 facilitates IL-18 production for the generation of protective antibodies against Candida albicans. Frontiers in microbiology, 11, 1648.
SINGH, S., VIJAYARAGHAVAN, P., DEVI, S. & HAMEED, S. 2024. An Update on Human Fungal Diseases: A Holistic Overview. Advances in Antifungal Drug Development: Natural Products with Antifungal Potential, 3-37.
STANISZEWSKA, M. 2020. Virulence factors in Candida species. Current Protein and Peptide Science, 21, 313-323.
VANPOUILLE, C., WELLS, A., WILKIN, T., MATHAD, J. S., MORRIS, S., MARGOLIS, L. & GIANELLA, S. 2022. Sex differences in cytokine profiles during suppressive antiretroviral therapy. Aids, 36, 1215-1222.
VERHOEF, J., VAN KESSEL, K. & SNIPPE, H. 2019. Immune response in human pathology: infections caused by bacteria, viruses, fungi, and parasites. Nijkamp and Parnham's Principles of Immunopharmacology. Springer.
VILA, T., SULTAN, A. S., MONTELONGO-JAUREGUI, D. & JABRA-RIZK, M. A. 2020. Oral candidiasis: A disease of opportunity. Journal of fungi, 6, 15.
ZHU, W., ZHANG, H., DONG, Q., SONG, H. & ZHAO, L. 2023. Dual wave of neutrophil recruitment determines the outcome of C. albicans infection. Frontiers in Cellular and Infection Microbiology, 13, 1239593.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Sawan M. Mirkhan, Taha J. Zrary
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors who choose to publish their work with Aro agree to the following terms:
-
Authors retain the copyright to their work and grant the journal the right of first publication. The work is simultaneously licensed under a Creative Commons Attribution License [CC BY-NC-SA 4.0]. This license allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
-
Authors have the freedom to enter into separate agreements for the non-exclusive distribution of the journal's published version of the work. This includes options such as posting it to an institutional repository or publishing it in a book, as long as proper acknowledgement is given to its initial publication in this journal.
-
Authors are encouraged to share and post their work online, including in institutional repositories or on their personal websites, both prior to and during the submission process. This practice can lead to productive exchanges and increase the visibility and citation of the published work.
By agreeing to these terms, authors acknowledge the importance of open access and the benefits it brings to the scholarly community.
Accepted 2026-01-11
Published 2026-04-10
ARO Journal is a scientific, peer-reviewed, periodical, and diamond OAJ that has no APC or ASC.