A review on the process immune system&#039;s interaction with mycobiota and pathogenic fungi

, Rafiee; , Karimi; Abdolahi Ziaaldini, Mohammad Amin; Nikoomanesh, Fatemeh

doi:10.66224/JBUMS.33.2.86

Volume 33, Issue 2 (6-2026) J Transl Med Res. 2026, 33(2): 86-98 | Back to browse issues page

‎ 10.66224/JBUMS.33.2.86

Research code: ندارد

Ethics code: ندارد

Clinical trials code: ندارد

Mendeley

Zotero

RefWorks

Abdolahi Ziaaldini M A, Nikoomanesh F. A review on the process immune system's interaction with mycobiota and pathogenic fungi. J Transl Med Res. 2026; 33 (2) :86-98
URL: http://journal.bums.ac.ir/article-1-3578-en.html

A review on the process immune system's interaction with mycobiota and pathogenic fungi

Mohammad Amin Abdolahi Ziaaldini¹

, Fatemeh Nikoomanesh ^*²

1- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
2- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran , fateme.nikoomanesh@bums.ac.ir

Abstract: (277 Views)

In recent years, the role of mycobiota as a fungal component of the human microbiota and its complex interactions with the immune system have become a major focus of immunology and infectious disease research. Increasing evidence suggests that mycobiota, in addition to maintaining mucosal homeostasis, plays a fundamental role in inducing immune tolerance, regulating inflammatory responses, maintaining the balance of microbial communities, and preventing colonization and invasion by opportunistic fungi. On the other hand, disruption of this balance in people with impaired or suppressed immune systems provides the basis for the development of invasive fungal infections caused by species, such as Candida, Aspergillus, and Cryptococcus. This review aimed to examine the findings related to the interaction between mycobiota, the host immune system, normal flora, and opportunistic fungi. In this regard, the mechanisms of recognition of fungal molecular patterns by pattern recognition receptors, immune signaling pathways, the role of phagocytic cells, Th1 and Th17 lymphocytes, and cytokines and key interleukins in response to fungal agents will be reviewed. The role of mycobiota in regulating mucosal immunity, the function of antibody responses, innate immune memory, and the consequences of disrupting these interactions in the development of inflammation and fungal infections are also discussed. On the other hand, examining the potential capacity of immune pathways can inform the design of new immunomodulatory strategies to control fungal infections. Overall, the available evidence shows that the balance between mycobiota, opportunistic fungi, and the immune system determines the transition from symbiosis to pathogenesis, and a detailed understanding of this complex network can pave the way for the development of new prevention strategies and modulation of the immune response against invasive fungal infections.

Keywords: Fungal infection, Immune response, Immune system, Mycobiota

Full-Text [PDF 509 kb] (83 Downloads) | | Full-Text (HTML) (32 Views)

Type of Study: Review | Subject: Mycology
Received: 2025/12/29 | Accepted: 2026/05/11 | ePublished: 2026/06/5

References

1. Underhill DM, Iliev ID. The mycobiota: interactions between commensal fungi and the host immune system. Nat Rev Immunol. 2014;14(6):405-16. DOI: 10.1038/nri3684 [DOI:10.1038/nri3684] [PMID] [PMCID]

2. Netea MG, Joosten LA, van der Meer JW, Kullberg BJ, Van De Veerdonk FL. Immune defence against Candida fungal infections. Nat Rev Immunol. 2015;15(10):630-42. DOI: 10.1038/nri3897 [DOI:10.1038/nri3897] [PMID]

3. Shao TY, Ang WXG, Jiang TT, Huang FS, Andersen H, Kinder JM, et al. Commensal Candida albicans positively calibrates host Th17 immunity. Cell Host Microbe. 2019;20(3):404-17. DOI: 10.1016/j.chom.2019.02.004 [DOI:10.1016/j.chom.2019.02.004] [PMID]

4. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121-41. DOI: 10.1016/j.cell.2014.03.011 [DOI:10.1016/j.cell.2014.03.011] [PMID] [PMCID]

5. 5 Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. Hidden killers: human fungal infections. Sci Transl Med. 2012;4(165):165rv13. DOI: 10.1126/scitranslmed.3004404 [DOI:10.1126/scitranslmed.3004404] [PMCID]

6. 6 Li XV, Leonardi I, Iliev ID. Gut mycobiota in immunity and inflammatory disease. Immunity. 2019;50(6):1365-79. DOI: 10.1016/j.immuni.2019.05.023 [DOI:10.1016/j.immuni.2019.05.023] [PMID] [PMCID]

7. 7 Plato A, Hardison S E, Brown GD. Pattern recognition receptors in antifungal immunity. Semin Immunopathol. 2015;37(2):97-106. DOI: 10.1007/s00281-014-0462-4 [DOI:10.1007/s00281-014-0462-4] [PMID] [PMCID]

8. 8 Sachdeva G, Das A. Communication between immune system and mycobiota impacts health and disease. Proc Indian Natl Sci Acad. 2022;88(3):250-62. DOI: 10.1007/s43538-022-00082-5 [DOI:10.1007/s43538-022-00082-5] [PMCID]

9. 9 Sen S, Mansell TJ. Yeasts as probiotics: mechanisms, outcomes, and future potential. Fungal Genet Biol. 2020;137:103333. DOI: 10.1016/j.fgb.2020.103333 [DOI:10.1016/j.fgb.2020.103333] [PMID]

10. 10 Pathakumari B, Liang G, Liu W. Biomedicine & Pharmacotherapy Immune defence to invasive fungal infections : A comprehensive review. Biomed Pharmacother. 2020;130(June):110550. DOI: 10.1016/j.biopha.2020.110550 [DOI:10.1016/j.biopha.2020.110550] [PMID]

11. 11 Saadati Z, Shahryari T, Ramazani AA, Sahlabadi F, Nikoomanesh F, Namaie MH. Investigation of Indoor and Outdoor Fungal Bioaerosols and Environmental Factors in Indoor Air Quality of Nursery SchoolsNo Title. Int J Mol Clin Microbiol. 2022;12(1):1596-604.URL: https://www.magiran.com/p2446735

12. 12 Mancuso G, Midiri A, Gerace E, Biondo C. Role of the innate immune system in host defence against fungal infections. Eur Rev Med Pharmacol Sci. 2022;1138-47.DOI: 10.26355/eurrev_202202_28105

13. 13 Shariati A, Moradabadi A, Chegini Z, Khoshbayan A,Didehdar M. An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies. Infect Drug Resist. 2020;13:2329-54. DOI: 10.2147/IDR.S254478 [DOI:10.2147/IDR.S254478] [PMID] [PMCID]

14. Zare-Bidaki M, Allahyari E, Nikoomanesh F, Ebrahimzadeh A.. A Comparative Analysis of Nosocomial Infections Between Internal and Surgical Intensive Care Units of University Hospitals in Birjand, Iran From 2016 to 2017: A Retrospective Study. J Basic Res Med Sci. 2021;8(4):32-41.DOI: 10.21203/rs.3.rs-42477/v1 [DOI:10.21203/rs.3.rs-42477/v1]

15. 15 Bergamasco MD, Pereira CAP, Arrais-Rodrigues C, Ferreira DB, Baiocchi O, Kerbauy F,et al. Epidemiology of Invasive Fungal Diseases in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation Recipients Managed with an Antifungal Diagnostic Driven Approach. J Fungi. 2021;7(8):588. DOI: 10.3390/jof7080588. [DOI:10.3390/jof7080588] [PMID] [PMCID]

16. 16 Souza L, Nouér SA, Morales H, Simões B, Solza C, Queiroz-Telles F, Nucci M. Epidemiology of invasive fungal disease in haematologic patients. Mycoses. 2021;64(3): 252-6. DOI: 10.1111/myc.13205 [DOI:10.1111/myc.13205] [PMID]

17. 17 Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 2021;6(291). DOI: 10.1038/s41392-021-00687-0 [DOI:10.1038/s41392-021-00687-0] [PMID] [PMCID]

18. 18 Patin EC, Thompson A, Orr SJ. Pattern recognition receptors in fungal immunity. Semin Cell Dev Biol. 2019;89:24-33. DOI: 10.1016/j.semcdb.2018.03.003. [DOI:10.1016/j.semcdb.2018.03.003] [PMID] [PMCID]

19. 19 Bourgeois C, Kuchler K. Fungal pathogens-a sweet and sour treat for toll-like receptors.Front Cell Infect Microbiol. 2012. 2:142. DOI: 10.3389/fcimb.2012.00142. [DOI:10.3389/fcimb.2012.00142] [PMID] [PMCID]

20. 20 Hardison SE, Brown GD. C-type lectin receptors orchestrate antifungal immunity. Nat Immunol. 2012;13(9):817-22. DOI: 10.1038/ni.2369. [DOI:10.1038/ni.2369] [PMID] [PMCID]

21. 21 Brouwer N, Dolman KM, van Houdt M, Sta M, Roos, Kuijpers TW. Mannose-binding lectin (MBL) facilitates opsonophagocytosis of yeasts but not of bacteria despite MBL binding. J Immunol. 2008;180(6):4124-32. DOI: 10.4049/jimmunol.180.6.4124. [DOI:10.4049/jimmunol.180.6.4124] [PMID]

22. 22 Alquraini A, El Khoury J. Scavenger receptors. Curr Biol [Internet]. 2020;30(14):R790-R795. DOI: 10.1016/j.cub.2020.05.051. [DOI:10.1016/j.cub.2020.05.051] [PMID] [PMCID]

23. 23 Choraghe RP, Neumann A. Dectin-1-Mediated DC-SIGN Recruitment to Candida albicans Contact Sites. Life Sci. 2021;11(2):108. DOI: 10.3390/life11020108 [DOI:10.3390/life11020108] [PMID] [PMCID]

24. 24 Romani L. Immunity to fungal infections. 2004;4(January): 1-23. DOI: 10.1038/nri1255 [DOI:10.1038/nri1255] [PMID]

25. 25 Shankar J, Thakur R, Clemons KV, Stevens DA. Interplay of Cytokines and Chemokines in Aspergillosis. J Fungi [Internet]. 2024;10(4):251.DOI: 10.3390/jof10040251 [DOI:10.3390/jof10040251] [PMID]

26. 26 Bidula S, Schelenz S. A Sweet Response to a Sour Situation: The Role of Soluble Pattern Recognition Receptors in the Innate Immune Response to Invasive Aspergillus fumigatus Infections. PLoS Pathog. 2016;12(e1005637). DOI: 10.1371/journal.ppat.1005637 [DOI:10.1371/journal.ppat.1005637] [PMID] [PMCID]

27. 27 Becker KL, Gresnigt MS, Smeekens SP, Jacobs CW, Magis-Escurra C, Jaeger M, et al. Pattern recognition pathways leading to a Th2 cytokine bias in allergic bronchopulmonary aspergillosis patients. Clin Exp Allergy. 2015;45(2):423-37. DOI: 10.1111/cea.12354 [DOI:10.1111/cea.12354] [PMID]

28. 28 Thakur R, Anand R, Tiwari S, Singh AP, Tiwary BN, Shankar J. Cytokines induce effector T-helper cells during invasive aspergillosis; what we have learned about T-helper cells? Front Microbiol. 2015;6:249. DOI: 10.3389/fmicb.2015.00429 [DOI:10.3389/fmicb.2015.00429]

29. 29 Ito Y, Takazono T, Obase Y, Fukahori S, Ashizawa N, Hirayama T, et al. Serum Cytokines Usefulness for Understanding the Pathology in Allergic Bronchopulmonary Aspergillosis and Chronic Pulmonary Aspergillosis. J Fungi. 2022;8(5):436. DOI: 10.3390/jof8050436 [DOI:10.3390/jof8050436] [PMID] [PMCID]

30. 30 Dewi IM, Van de Veerdonk FL, Gresnigt MS. The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus fumigatus. J Fungi. 2017;3(4):55. DOI: 10.3390/jof3040055 [DOI:10.3390/jof3040055] [PMID] [PMCID]

31. 31 Puerta-Arias JD, Mejía SP, González Á. The Role of the Interleukin-17 Axis and Neutrophils in the Pathogenesis of Endemic and Systemic Mycoses. Front Cell Infect Microbiol. 2020;10(595301). DOI: 10.3389/fcimb.2020.595301 [DOI:10.3389/fcimb.2020.595301] [PMID] [PMCID]

32. 32 Roudbary M, Kumar S, Kumar A, Cern L, Nikoomanesh F, Rodrigues CF. Overview on the Prevalence of Fungal Infections, Immune Response, and Microbiome Role in COVID-19 Patients. 2021;(Figure 1):1-28. DOI: 10.3390/jof7090720 [DOI:10.3390/jof7090720] [PMID]

33. 33 Cheng KO, Montaño DE, Zelante T, Dietschmann A GM. Inflammatory cytokine signalling in vulvovaginal candidiasis: a hot mess driving immunopathology. Oxf Open Immunol. 2024;5(1):iqae010. DOI: 10.1093/oxfimm/iqae010. [DOI:10.1093/oxfimm/iqae010] [PMID]

34. 34 Kumaresan PR, Da Silva TA, Kontoyiannis DP. Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells. Front Immunol. 2017;8(1939). DOI: 10.3389/fimmu.2017.01939 [DOI:10.3389/fimmu.2017.01939] [PMID] [PMCID]

35. 35 Mengesha BG, Conti HR. The Role of IL-17 in Protection against Mucosal Candida Infections. J Fungi. 2017;3(4):52. DOI: 10.3390/jof3040052 [DOI:10.3390/jof3040052] [PMID] [PMCID]

36. 36 Pellon A, Sadeghi Nasab SD, Moyes DL. New insights in Candida albicans innate immunity at the mucosa: toxins, epithelium, metabolism, and beyond. Front Cell Infect Microbiol. 2020;3(10):81. DOI: 10.3389/fcimb.2020.00081 [DOI:10.3389/fcimb.2020.00081] [PMID] [PMCID]

37. 37 Moyes DL, Shen C, Murciano C, Runglall M, Richardson JP, Arno M, et al. Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling. J Infect Dis. 2014;209(1):1816-26. DOI: 10.1093/infdis/jit824 [DOI:10.1093/infdis/jit824] [PMID] [PMCID]

38. 38 Zhou Y, Cheng L, Lei YL, Ren B, Zhou X. The interactions between Candida albicans and mucosal immunity. Front Microbiol. 2021;12(652725). DOI: 10.3389/fmicb.2021.652725 [DOI:10.3389/fmicb.2021.652725] [PMID] [PMCID]

39. 39 Wich M, Greim S, Ferreira-Gomes M, Krüger T, Kniemeyer O, Brakhage AA, et al. Functionality of the human antibody response to Candida albicans. Virulence. 2021;12(1):3137-48. DOI: 10.1080/21505594.2021.2015116 [DOI:10.1080/21505594.2021.2015116] [PMID] [PMCID]

40. 40 Doron I, Leonardi I, Li XV, Fiers WD, Semon A, Bialt-DeCelie M, et al. Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies. Cell. 2021;184(4):1017-31. DOI: 10.1016/j.cell.2021.01.016 [DOI:10.1016/j.cell.2021.01.016] [PMID]

41. 41 Swidergall M,LeibundGut-Landmann S. Immunosurveillance of Candida albicans commensalism by the adaptive immune system. Mucosal Immunol. 2022;15(5):829-36. DOI: 10.1038/s41385-022-00536-5 [DOI:10.1038/s41385-022-00536-5] [PMID] [PMCID]

42. 42 Millet N, Solis NV, Swidergall M. Mucosal IgA prevents commensal Candida albicans dysbiosis in the oral cavity. Front Immunol. 2020;11(555363). DOI: 10.3389/fimmu.2020.555363 [DOI:10.3389/fimmu.2020.555363] [PMID] [PMCID]