Role of IL-22 and TNF-α in pulmonary candidiasis and its effects as immunomodulation through Dectin-2 receptor mediation
Article Main
Abstract
Pulmonary fungal infections are severe and potentially fatal conditions caused by various fungi, with varying levels of seriousness. The present study aimed to determine the immunomodulatory role of IL-22 and TNF-α in patients with pulmonary candidiasis. Sputum specimens from 106 (Male/Female) outpatients were collected at the Consultation Clinic for Chest and Respiratory Diseases in Salah Al-Din Governorate in Tikrit – Iraq, from June 2022 to December 2022. The age groups ranged from 20 -75 years. Phenotypic identification of isolates was performed based on Gram reaction, direct wet preparation (10% KOH), and HiCrome™ candida differential agar. Complete species identification was confirmed using the Vitek2® compact system. The study patients' stimulation of IL-22 and TNF-α production through the 4Dectin-2 (CLEC6A) receptor was also examined. The results revealed that 40 of the collected specimens (37.7%) were confirmed as Candida. albicans. Dectin-2 (CLEC6A) expression indicates the concurrent release of TNF-α and IL-22 cytokines in response to C. albicans. The study determined that C. albicans was the main cause of pulmonary candidiasis. These findings can provide valuable insights to optimize the treatment strategies, ultimately enhancing the patient’s quality of life.
Article Details
Article Details
Keywords
Candida albicans, Dectin-2, IL-22, Pulmonary fungal infections, Tumor Necrosis Factor-α
References
Abdulateef S. M., Ibraheem S., Hussein H S., Dheeb BI., Khashman B.M., Ahmed D.M. & Abu-Elteen KH . (2024). MMP-1 and MMP-7 expression is influenced by ginsenosides in mice exposed to aflatoxin B1: in vivo study. Jordan J Pharm Sci.,17 (1): 135-1139.
Abdullah HI, Hammadi SY, Hussein AS & Dheeb B.I.(2019). Investigation of genetic diversity and relationships among the clinical Candida species using random amplified polymorphic DNA (RAPD) analysis., Research Journal of Biotechnology., 14(1):6–13.
Abed SM, Farhan MG, Madhloom NK & Dheeb BI. (2022). Magnetic field exposure to clinical isolates of Acinitobacter baumanii. Biomed Pharmacol J., 15(4): 2137–2143.
Al Zaher RM., Abderrahman SM., Abdulateef SM., Dheeb BI., Massadeh MI, Hussein AS. & Farhan MS . 2024. Antimicrobial activity of Zn-nanoparticles synthesized by leaf extract of Capparis spinosa. Research Journal Biotechnology., 19(11).639.
Albrecht M., Halle O., Gaedcke S., Pallenberg S.T., Camargo Neumann J., Witt M., Roediger, J., Schumacher, M., Jirmo, A.C., Warnecke, G., Jonigk, D., Braubach, P., DeLuca, D., Hansen, G. & Dittrich, A-M. (2022). Interleukin-17A and interleukin-22 production by conventional and non-conventional lymphocytes in three different end-stage lung diseases. Clinical & Trans Immunology,11.1–18. https://doi.org/10.1002/cti2.1398.
Al-Sarraj BM, Salman RD, Ahmed DM, Massadeh MI, & Dheeb BI. (2024). Bacteriological and molecular detection of fluoroquinolone resistance in Escherichia coli isolated from women patients with urinary tract infections. Farmacia.,72(4):840-847.
Bhattacharya S., Sae-Tia S.& Fries B.C. (2020). Candidiasis and mechanisms of antifungal resistance. Antibiotics, 9,1–19. https://doi.org/10.3390/antibiotics9060312.
Bruno M., Kersten S., Bain J. M., Jaeger M., Rosati D., Kruppa M. D.,Lowman, D.W., Rice, P.J., Graves, B., Ma, Z., Jiao, Y.N., Chowdhary, A., Renieris, G., van de Veerdonk, F., Kullberg, B-J., Giamarellos-Bourboulis,E.J., Hoischen, A., Gow, N.A.R., Brown, A.J.P., Meis, J.F., Williams, D.L & Netea, M.G. (2020). Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris. Nature Microbiol, 5(12), 1516–1531. https:// doi: 10.1038/s41564-020-0780-3.
Dadar M., Tiwari R., Karthik K., Chakraborty S., Shahali Y.& Dhama K. (2018), Candida albicans - Biology, molecular characterization, pathogenicity, and advances in diagnosis and control – An update. Microbial Pathogenesis, 117,128-138 https://doi.org/10.1016/j.micpath.2018.02.028.
Davidson, L., Netea M.G. & Kullberg B.J. (2018). Patient Susceptibility to Candidiasis A Potential for Adjunctive Immunotherapy. Journal of Fungi. 4(1),9 https://doi.org/10.3390/jof4010009
de Jong, M.A.W.P., Vriend, L.E.M., Theelen, B., Taylor, M.E., Fluitsma, D., Boekhout, T., & Geijtenbeek, T.B.H. (2010). C-type lectin Langerin is a β-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi. Molecular Immunology, 47,:1216–1225 https://doi.org/10.1016/j.molimm.2009.12.016.
De Luca, A., Zelante, T., D’Angelo, C., Zagarella, S., Fallarino, F., Spreca, A., Iannitti, R.G., Bonifazi, P., Renauld, J-C., Bistoni, F., Puccetti, P & Romani, L. (2010). IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunology, 3(4), 361–373. https://doi.org/10.1038/mi.2010.22.
Dheeb B I, Abdulla S N, AL-Qaysi SAS, Al-Sarraj BM & Farhan MS. 2023. Extraction of Klebsiella pneumoniae and Candida albicans biofilm and studying their cytotoxic effects on human lymphocytes. Jordan J Biol Sci., 16(4):717–726.https://doi.org/10.54319/jjbs/160418
Galocha, M., Pais, P., Cavalheiro, M., Pereira, D., Viana, R. & Teixeira M.C. (2019). Divergent approaches to virulence in C. albicans and C. glabrata: Two sides of the same coin. International Journal of Molecular Science,20 (9), 2345. https://doi.org/10.3390/ijms 20092345.
Goyal, S., Castrillon-Betancur, J.C., Klaile, E. & Slevogt H. (2018). The interaction of human pathogenic fungi with C-Type lectin receptors. Frontiers Immunology, 9, 1261 https://doi.org/10.3389/fimmu.2018.01261.
Hashim S S, Mahmood Z F, Abdulateef SM. & Dheeb BI. 2023. Evaluation cytotoxicity effects of Centaurea cineraria extracts against some of cancer cell lines. Biomed Pharmacol Journal .16(1): 243–249.
Hassan, Y., Chew, S.Y. & Than L.T.L. (2021). Candida glabrata: Pathogenicity and resistance mechanisms for adaptation and survival. Journal of Fungi, 7 (8), 667 https://doi.org/10.3390/jof 7080667.
Hatem YQ & Dheeb BI. (2024). Cytotoxic effects of Gliotoxin extracted from Candida albicans isolated from patients with urinary tract infection. MCB , 21(2),1-12. https://doi.org/10.62617/mcb639
Hussain AF, Sulaiman GM, Dheeb BI, and Hashim AJ, Abd Alrahman ES, Seddiq SH & Khashman BM. 2020. Histopathological changes and expression of transforming growth factor beta (TGF-β3) in mice exposed to gliotoxin, J King Saud University – Science, 32(1): 716–725.
Jaszczura, M., Mizgała-Izworska, E., Świętochowska, E. & Machura, E. (2019). Serum levels of selected cytokines [interleukin (IL)-17A, IL-18, IL-23] and chemokines (RANTES, IP10) in the acute phase of immunoglobulin A vasculitis in children. Rheumatology International,39(11),1945-1953. doi: 10.1007/s00296-019-04415-4.
Johnson, M.D., Plantinga, T.S., Vosse, E. van de, Edwards, D.R.V., Smith P.B., Alexander, B.D., Yang, J.C., Kremer, D., Laird, G.M., Oosting, M., Joosten, L.A.B., van der Meer, J.W.M., van Dissel, J. T., Walsh, T.J., Perfect, J.R., Kullberg, B-J., Scott, W.K & Netea, M.G. (2012). Cytokine gene polymorphisms and the outcome of invasive candidiasis : A prospective cohort study. Clinical Infectious Diseases, 54(4),502-510. https://doi.org/10.1093/cid/cir827.
Kühbacher, A., Burger-kentischer, A. & Rupp S. (2017). Interaction of Candida species with the skin. Microorganisms, 5(2), 32. https://doi.org/10.3390/microorganisms5020032
Li, Z., Lu, G. & Meng, G. (2019). Pathogenic fungal infection in the lung. Frontiers Immunology, 10:1524. https://doi.org/10.3389/fimmu.2019.01524
Ma, Q., Luan, J., Bai, Y., Xu, C., Liu, F. & Chen, B. (2022). Interleukin-22 in renal protection and its pathological role in kidney diseases. Frontiers Immunology, 13(78), 45-50. https://doi.org/10.3389/fimmu.2022.851818
Netea, M.G., Joosten, L.A.B., Van Der Meer, J.W.M., Kullberg, B.J. & Van De Veerdonk, F.L. (2015). Immune defence against Candida fungal infections. Nature Reviews Immunology, 15,630–642. https://doi.org/10.1038/nri3897
Nett, J.E. & Andes, D.R. (2020). Contributions of the biofilm matrix to Candida pathogenesis. Journal of Fungi, 6,33–38. https://doi.org/10.3390/jof6010021.
Pietrzak, A., Grywalska, E., Socha, M., Rolinski, J., Franciszkiewicz-Pietrzak K., Rudnicka L., Rudzki, M & Krasowska, D. (2018). Prevalence and possible role of Candida species in patients with psoriasis: A systematic review and meta-analysis. Mediators of Inflammation, 2018, Article ID 9602362 https://doi.org/10.1155/2018/9602362
Sato, Y., Sato, K., Yamamoto, H., Kasamatsu, J., Miyasaka, T., Tanno, D.,Miyahara, A., Kagesawa, T., Oniyama, A., Kawamura, K., Yokoyama, R., Kitai, Y., Umeki, A., Ishizuka,S., Takano, K., Shiroma, R., Nakahata, N., Kawakami, K., Kanno, E., Tanno, H., Yamasaki, S., Hara, H. Ishii, K. & Kawakami, K.(2020). Limited role of mincle in the host defense against infection with Cryptococcus deneoformans. Infection and Immunity, 88 (11), e00400-20.https://doi.org/10.1128/IAI.00400-20.
Shohan, M., Dehghani, R., Khodadadi, A., Dehnavi, S., Ahmadi R., Joudaki, N., Houshmandfar, S., Shamshiri, M., Shojapourian, S.& Bagheri, N. (2020). Interleukin-22 and intestinal homeostasis: Protective or destructive? International Union of Biochemistry and Molecular Biology Life, 72:1585–1602. https://doi.org/10.1002/iub.2295
Smith, D., Midgley, J. & Gazzard, B. (1999). A randomised, double-blind study of itraconazole versus placebo in the treatment and prevention of oral or oesophageal candidosis in patients with HIV infection. International Journal of Clinical Practice, 53(5),349-352.
Tanwar, P., Naagar, M. & Maity, M.K. (2023). Role of Pathogens in Pulmonary Fungal Infection – A Review. International Journal of Enhanced Research in Medicines & Dental Care,10 (1), 41-60.
Thompson, A., da Fonseca, D.M., Walker, L., Griffiths, J.S., Taylor, P.R., Gow, N.A.R. & Orr, S.J. (2021). Dependence on mincle and dectin-2 varies with multiple Candida species during systemic infection. Frontiers in Microbiology, 12,633229.
Vacher, G., Niculita-Hirzel, H.& Roger, T. (2015). Immune responses to airborne fungi and non-invasive airway diseases. Semin Immunopathology, 37,83–96.
Wang, Y. (2015). Looking into Candida albicans infection, host response, and antifungal strategies. Virulence,
6,307–308. https://doi.org/10.1080/21505594.2014.100 0752
Wang, Y., Zou, Y., Chen, X., Li, H., Yin, Z., Zhang, B.,Xu, Y., Zhang, Y., Zhang, R., Huang, X., Yang, W., Xu, C., Jiang, T., Tang, Q., Zhou, Z., Ji, Y., Hu, Y., Hu, L., Zhou, J., Zhou, Y., Zhao, J., Liu, N., Huang, G., Chang, H., Fang, W., Chen, C. & Zhou, D.(2022). Innate immune responses against the fungal pathogen Candida auris . Nature Communications, 13(1):3553. https://doi.org/10.1 038/s41467-022-31201-x.
Yahaya, H. & Sule, H. (2023). Candida auris: an emergent virulent and multidrug-resistant yeast associated with serious health implications. Academia Biology, 2023;1. https://doi.org/10.20935/AcadBiol6074
Abdullah HI, Hammadi SY, Hussein AS & Dheeb B.I.(2019). Investigation of genetic diversity and relationships among the clinical Candida species using random amplified polymorphic DNA (RAPD) analysis., Research Journal of Biotechnology., 14(1):6–13.
Abed SM, Farhan MG, Madhloom NK & Dheeb BI. (2022). Magnetic field exposure to clinical isolates of Acinitobacter baumanii. Biomed Pharmacol J., 15(4): 2137–2143.
Al Zaher RM., Abderrahman SM., Abdulateef SM., Dheeb BI., Massadeh MI, Hussein AS. & Farhan MS . 2024. Antimicrobial activity of Zn-nanoparticles synthesized by leaf extract of Capparis spinosa. Research Journal Biotechnology., 19(11).639.
Albrecht M., Halle O., Gaedcke S., Pallenberg S.T., Camargo Neumann J., Witt M., Roediger, J., Schumacher, M., Jirmo, A.C., Warnecke, G., Jonigk, D., Braubach, P., DeLuca, D., Hansen, G. & Dittrich, A-M. (2022). Interleukin-17A and interleukin-22 production by conventional and non-conventional lymphocytes in three different end-stage lung diseases. Clinical & Trans Immunology,11.1–18. https://doi.org/10.1002/cti2.1398.
Al-Sarraj BM, Salman RD, Ahmed DM, Massadeh MI, & Dheeb BI. (2024). Bacteriological and molecular detection of fluoroquinolone resistance in Escherichia coli isolated from women patients with urinary tract infections. Farmacia.,72(4):840-847.
Bhattacharya S., Sae-Tia S.& Fries B.C. (2020). Candidiasis and mechanisms of antifungal resistance. Antibiotics, 9,1–19. https://doi.org/10.3390/antibiotics9060312.
Bruno M., Kersten S., Bain J. M., Jaeger M., Rosati D., Kruppa M. D.,Lowman, D.W., Rice, P.J., Graves, B., Ma, Z., Jiao, Y.N., Chowdhary, A., Renieris, G., van de Veerdonk, F., Kullberg, B-J., Giamarellos-Bourboulis,E.J., Hoischen, A., Gow, N.A.R., Brown, A.J.P., Meis, J.F., Williams, D.L & Netea, M.G. (2020). Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris. Nature Microbiol, 5(12), 1516–1531. https:// doi: 10.1038/s41564-020-0780-3.
Dadar M., Tiwari R., Karthik K., Chakraborty S., Shahali Y.& Dhama K. (2018), Candida albicans - Biology, molecular characterization, pathogenicity, and advances in diagnosis and control – An update. Microbial Pathogenesis, 117,128-138 https://doi.org/10.1016/j.micpath.2018.02.028.
Davidson, L., Netea M.G. & Kullberg B.J. (2018). Patient Susceptibility to Candidiasis A Potential for Adjunctive Immunotherapy. Journal of Fungi. 4(1),9 https://doi.org/10.3390/jof4010009
de Jong, M.A.W.P., Vriend, L.E.M., Theelen, B., Taylor, M.E., Fluitsma, D., Boekhout, T., & Geijtenbeek, T.B.H. (2010). C-type lectin Langerin is a β-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi. Molecular Immunology, 47,:1216–1225 https://doi.org/10.1016/j.molimm.2009.12.016.
De Luca, A., Zelante, T., D’Angelo, C., Zagarella, S., Fallarino, F., Spreca, A., Iannitti, R.G., Bonifazi, P., Renauld, J-C., Bistoni, F., Puccetti, P & Romani, L. (2010). IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunology, 3(4), 361–373. https://doi.org/10.1038/mi.2010.22.
Dheeb B I, Abdulla S N, AL-Qaysi SAS, Al-Sarraj BM & Farhan MS. 2023. Extraction of Klebsiella pneumoniae and Candida albicans biofilm and studying their cytotoxic effects on human lymphocytes. Jordan J Biol Sci., 16(4):717–726.https://doi.org/10.54319/jjbs/160418
Galocha, M., Pais, P., Cavalheiro, M., Pereira, D., Viana, R. & Teixeira M.C. (2019). Divergent approaches to virulence in C. albicans and C. glabrata: Two sides of the same coin. International Journal of Molecular Science,20 (9), 2345. https://doi.org/10.3390/ijms 20092345.
Goyal, S., Castrillon-Betancur, J.C., Klaile, E. & Slevogt H. (2018). The interaction of human pathogenic fungi with C-Type lectin receptors. Frontiers Immunology, 9, 1261 https://doi.org/10.3389/fimmu.2018.01261.
Hashim S S, Mahmood Z F, Abdulateef SM. & Dheeb BI. 2023. Evaluation cytotoxicity effects of Centaurea cineraria extracts against some of cancer cell lines. Biomed Pharmacol Journal .16(1): 243–249.
Hassan, Y., Chew, S.Y. & Than L.T.L. (2021). Candida glabrata: Pathogenicity and resistance mechanisms for adaptation and survival. Journal of Fungi, 7 (8), 667 https://doi.org/10.3390/jof 7080667.
Hatem YQ & Dheeb BI. (2024). Cytotoxic effects of Gliotoxin extracted from Candida albicans isolated from patients with urinary tract infection. MCB , 21(2),1-12. https://doi.org/10.62617/mcb639
Hussain AF, Sulaiman GM, Dheeb BI, and Hashim AJ, Abd Alrahman ES, Seddiq SH & Khashman BM. 2020. Histopathological changes and expression of transforming growth factor beta (TGF-β3) in mice exposed to gliotoxin, J King Saud University – Science, 32(1): 716–725.
Jaszczura, M., Mizgała-Izworska, E., Świętochowska, E. & Machura, E. (2019). Serum levels of selected cytokines [interleukin (IL)-17A, IL-18, IL-23] and chemokines (RANTES, IP10) in the acute phase of immunoglobulin A vasculitis in children. Rheumatology International,39(11),1945-1953. doi: 10.1007/s00296-019-04415-4.
Johnson, M.D., Plantinga, T.S., Vosse, E. van de, Edwards, D.R.V., Smith P.B., Alexander, B.D., Yang, J.C., Kremer, D., Laird, G.M., Oosting, M., Joosten, L.A.B., van der Meer, J.W.M., van Dissel, J. T., Walsh, T.J., Perfect, J.R., Kullberg, B-J., Scott, W.K & Netea, M.G. (2012). Cytokine gene polymorphisms and the outcome of invasive candidiasis : A prospective cohort study. Clinical Infectious Diseases, 54(4),502-510. https://doi.org/10.1093/cid/cir827.
Kühbacher, A., Burger-kentischer, A. & Rupp S. (2017). Interaction of Candida species with the skin. Microorganisms, 5(2), 32. https://doi.org/10.3390/microorganisms5020032
Li, Z., Lu, G. & Meng, G. (2019). Pathogenic fungal infection in the lung. Frontiers Immunology, 10:1524. https://doi.org/10.3389/fimmu.2019.01524
Ma, Q., Luan, J., Bai, Y., Xu, C., Liu, F. & Chen, B. (2022). Interleukin-22 in renal protection and its pathological role in kidney diseases. Frontiers Immunology, 13(78), 45-50. https://doi.org/10.3389/fimmu.2022.851818
Netea, M.G., Joosten, L.A.B., Van Der Meer, J.W.M., Kullberg, B.J. & Van De Veerdonk, F.L. (2015). Immune defence against Candida fungal infections. Nature Reviews Immunology, 15,630–642. https://doi.org/10.1038/nri3897
Nett, J.E. & Andes, D.R. (2020). Contributions of the biofilm matrix to Candida pathogenesis. Journal of Fungi, 6,33–38. https://doi.org/10.3390/jof6010021.
Pietrzak, A., Grywalska, E., Socha, M., Rolinski, J., Franciszkiewicz-Pietrzak K., Rudnicka L., Rudzki, M & Krasowska, D. (2018). Prevalence and possible role of Candida species in patients with psoriasis: A systematic review and meta-analysis. Mediators of Inflammation, 2018, Article ID 9602362 https://doi.org/10.1155/2018/9602362
Sato, Y., Sato, K., Yamamoto, H., Kasamatsu, J., Miyasaka, T., Tanno, D.,Miyahara, A., Kagesawa, T., Oniyama, A., Kawamura, K., Yokoyama, R., Kitai, Y., Umeki, A., Ishizuka,S., Takano, K., Shiroma, R., Nakahata, N., Kawakami, K., Kanno, E., Tanno, H., Yamasaki, S., Hara, H. Ishii, K. & Kawakami, K.(2020). Limited role of mincle in the host defense against infection with Cryptococcus deneoformans. Infection and Immunity, 88 (11), e00400-20.https://doi.org/10.1128/IAI.00400-20.
Shohan, M., Dehghani, R., Khodadadi, A., Dehnavi, S., Ahmadi R., Joudaki, N., Houshmandfar, S., Shamshiri, M., Shojapourian, S.& Bagheri, N. (2020). Interleukin-22 and intestinal homeostasis: Protective or destructive? International Union of Biochemistry and Molecular Biology Life, 72:1585–1602. https://doi.org/10.1002/iub.2295
Smith, D., Midgley, J. & Gazzard, B. (1999). A randomised, double-blind study of itraconazole versus placebo in the treatment and prevention of oral or oesophageal candidosis in patients with HIV infection. International Journal of Clinical Practice, 53(5),349-352.
Tanwar, P., Naagar, M. & Maity, M.K. (2023). Role of Pathogens in Pulmonary Fungal Infection – A Review. International Journal of Enhanced Research in Medicines & Dental Care,10 (1), 41-60.
Thompson, A., da Fonseca, D.M., Walker, L., Griffiths, J.S., Taylor, P.R., Gow, N.A.R. & Orr, S.J. (2021). Dependence on mincle and dectin-2 varies with multiple Candida species during systemic infection. Frontiers in Microbiology, 12,633229.
Vacher, G., Niculita-Hirzel, H.& Roger, T. (2015). Immune responses to airborne fungi and non-invasive airway diseases. Semin Immunopathology, 37,83–96.
Wang, Y. (2015). Looking into Candida albicans infection, host response, and antifungal strategies. Virulence,
6,307–308. https://doi.org/10.1080/21505594.2014.100 0752
Wang, Y., Zou, Y., Chen, X., Li, H., Yin, Z., Zhang, B.,Xu, Y., Zhang, Y., Zhang, R., Huang, X., Yang, W., Xu, C., Jiang, T., Tang, Q., Zhou, Z., Ji, Y., Hu, Y., Hu, L., Zhou, J., Zhou, Y., Zhao, J., Liu, N., Huang, G., Chang, H., Fang, W., Chen, C. & Zhou, D.(2022). Innate immune responses against the fungal pathogen Candida auris . Nature Communications, 13(1):3553. https://doi.org/10.1 038/s41467-022-31201-x.
Yahaya, H. & Sule, H. (2023). Candida auris: an emergent virulent and multidrug-resistant yeast associated with serious health implications. Academia Biology, 2023;1. https://doi.org/10.20935/AcadBiol6074
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Role of IL-22 and TNF-α in pulmonary candidiasis and its effects as immunomodulation through Dectin-2 receptor mediation. (2025). Journal of Applied and Natural Science, 17(2), 472-478. https://doi.org/10.31018/jans.v17i2.6325
