Dear Colleagues,

Candidiasis is an opportunistic infection caused mainly by C. albicans, a commensal fungus that asymptomatically colonizes ~60% of healthy individuals. Cancer treatments, genetic causes, and immunodeficiency (as in HIV infection) pre-dispose individuals to chronic and recurrent mucocutaneous candidiasis [1,2], causing secondary complications including squamous cell carcinoma and aneurysms [3]. With an alarming increase in biofilm infections associated with dentures and medical devices and anti-fungal drug resistance [4], there is a pressing need to develop new immuno-therapeutics. Candidiasis, in vaginal mucosa can also lead to neutrophil-mediated immunopathology in some instances, but the mechanisms are unclear. Notably, antibiotics increase the risk for mucosal and disseminated candidiasis in humans and mice and the immune mechanisms are just beginning to be explored [5–10]. Apart from the direct TLR-2 and C-type lectin receptor-dependent innate immune signals, recent studies have established the roles of tissue-resident Th17 cells, regulatory T cells, and IgA production in conveying an effective anti-Candidal immune response to maintain commensalism [11–14]. Candidalysin, a toxin produced by tissue-damaging hyphae of Candida. sp has been implicated in the establishment of IL-1- and IL-17-dependent innate immunity, although its interaction with adaptive immunity and its role in the other mentioned diseases remain to be investigated [15]. Oral fungal microbiome (mycobiome) could play a critical role in modulating many human diseases such as periodontal disease, IBD, and cancer, but the mechanistic relationships are not well characterized. Similarly, the vaginal mycobiome may impact health and disease far beyond vulvovaginal candidiasis. Older adults have increased oral colonization, opportunistic infections, and increased anti-fungal resistance. Recent studies are just beginning to explore some of the underlying mechanisms [16], but new studies furthering research along these directions are warranted.

This Special Issue will cover diverse aspects of these topics. All types of articles will be considered for publication, including short reports, primary research articles, and reviews. We look forward to your contribution.

Reference

1. Cheng, S.C.; Joosten, L.A.; Kullberg, B.J.; Netea, M.G. Interplay between Candida albicans and the mammalian innate host defense. Immun. 2012, 80, 1304–1313
2. Marodi, L.; Johnston, R.B., Jr. Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms. Opin. Pediatrics 2007, 19, 693–697
3. Huppler, A.R.; Bishu, S.; Gaffen, S.L. Mucocutaneous candidiasis: the IL-17 pathway and implications for targeted immunotherapy. Arthritis Res. Ther. 2012, 14, 217.
4. Gulshan, K.; Moye-Rowley, W.S. Multidrug resistance in fungi. cell 2007, 6, 1933–1942.
5. Bhaskaran, N.; Quigley, C.; Paw,C.; Butala, S.; Schneider,E.; Pandiyan, P. Role of Short Chain Fatty Acids in Controlling Tregs and Immunopathology During Mucosal Infection. Front Microbiol 2018, 9, 1995.
6. Pandiyan, P.; Bhaskaran, N.; Zou, M.; Schneider, E.; Jayaraman, S.; Huehn, J. Microbiome dependent regulation of Tregs and Th17 cells in mucosa. Front Immunol 2019, 3.
7. Peleg, A.Y.; Hogan, D.A.; Mylonakis, E. Medically important bacterial-fungal interactions. Nature Rev. Microbiol. 2010, 8, 340–349.
8. Kennedy, M.J.; Volz, P.A. Ecology of Candida albicans gut colonization: inhibition of Candida adhesion, colonization, and dissemination from the gastrointestinal tract by bacterial antagonism. Immun. 1985, 49, 654–663.
9. Kennedy, M.J.; Volz, P.A.; Edwards, C.A.; Yancey, R.J. Mechanisms of association of Candida albicans with intestinal mucosa. Med Microbiol. 1987, 24, 333–341.
10. Nord, C.E.; Heimdahl, A.; Kager, L. Antimicrobial induced alterations of the human oropharyngeal and intestinal microflora. J. Infect. Dis. Suppl. 1986, 49, 64–72.
11. Kirchner, F.R.; LeibundGut-Landmann, S. Tissue-resident memory Th17 cells maintain stable fungal commensalism in the oral mucosa. Mucosal Immunol 2020, 7.
12. Pandiyan, P.; Conti, H.R.; Zheng, L.; Peterson, A.C.; Mathern, D.R.; Hernández-Santos, N.; Edgerton, M.; Gaffen, S.L.; Lenardo, M.J. CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection model. Immunity 2011, 34, 422–434.
13. Conti, H.R.; Shen, F.; Nayyar, N.; Stocum, E. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 2009, 206, 299–311.
14. Millet, N.; Solis, N.V.; Swidergall, M. Mucosal IgA Prevents Commensal Candida albicans Dysbiosis in the Oral Cavity. Front Immunol 2020, 11, 555363.
15. Ho, J.; Camilli, G.; Griffiths, J.S.; Richardson, J.P.; Kichik, N.; Naglik, J.R. Candida albicans and candidalysin in inflammatory disorders and cancer. Immunology 2021, 162, 11–16
16. Bhaskaran, N.; Faddoul, F.; da Silva, A.P.; Jayaraman, S.; Schneider, E.; Mamileti, P.; Weinberg, A.; Pandiyan, P. IL-1beta-MyD88-mTOR Axis Promotes Immune-Protective IL-17A(+)Foxp3(+) Cells During Mucosal Infection and Is Dysregulated With Aging. Front Immunol 2020, 11, 595936.

Dr. Pushpa Pandiyan
Guest Editor
Prof. Dr. Salomé LeibundGut-Landmann
Co-Guest Editor

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• Candida
• fungal microbiome
• mycobiome
• chronic inflammation
• periodontal disease
• fungi in cancers