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New Insights into Current Understanding of Host–Fungal Interactions
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New Insights into Current Understanding of Host–Fungal Interactions

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 19849

Special Issue Editors

Prof. Dr. Jürgen Löffler

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Guest Editor
Department of Internal Medicine II, University Hospital of Würzburg, 97070 Würzburg, Germany
Interests: innate immunity, infection, inflammation; invasive aspergillosis; aspergillus fumigatus
Special Issues, Collections and Topics in MDPI journals
Dr. Agostinho Carvalho

E-Mail Website
Guest Editor
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
Interests: host–fungus interactions; antifungal immunity; genetics of susceptibility; personalized medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Thomas Rogers

E-Mail Website
Guest Editor
Department of Clinical Microbiology, Trinity College Dublin, St James’s Hospital Campus, Dublin, Ireland
Interests: invasive fungal infections; host-pathogen interactions; antifungal therapies; invasive pulmonary aspergillosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Invasive fungal infections are a major threat worldwide. They are associated with unacceptably high mortality rates ranging from 30–90% and have been estimated to kill about 1.5 million people every year globally. They are no longer limited to well-defined high-risk patient groups but affect, for example, patients treated with immune modulators or genetically modified cells and patients suffering from severe influenza infections, COVID-19. Options for antifungal therapy remain limited and mainly rely on three classes of antifungals. In addition, we are faced with increasing antifungal drug resistance.

Fungal pathogens are ubiquitous in the environment but are also important constituents of the human microflora. They thereby differ significanty from other pathogens, because eukaryotes are more closely related to humans and harbor unique immunogenic molecules such as ß-glucan or chitin, which are absent in prokaryotic pathogens.

Fungi have unique interaction patterns with human hosts. Detailed characterization of host–fungal interactions is necessary in order to gain a better understanding of the immune response directed against fungi and how to exploit it in diagnostic and therapuetic interventions.

With this Special Issue of the Journal of Fungi, we aim to publish a collection of articles that will showcase and provide new insights into current understanding of host–fungal interactions. This will include original articles and reviews. Examples for relevant topics are new emerging fungal species, the influence of immune modulators, small molecules and genetically engineered immune cells on the development of fungal infections, immunization against fungal pathogens, fungal–viral co-infections (such as influenza and SARS-CoV2), and the role of specific host biomarkers in fungal infections (such as SNPs, eQTLs, and miRNA). Another focus is preclincial models (in vitro or in vivo) describing fundamental aspects of the host–fungus interaction, with emphasis on both sides of the interaction.

We are pleased to invite you to submit your manuscripts on these new aspects of host–fungal interactions that will reveal a greater innovative insight into these emerging topics.

Prof. Dr. Jürgen Löffler
Dr. Agostinho Carvalho
Prof. Dr. Thomas Rogers
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • host–fungal interactions
  • new insights
  • immune response

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Related Special Issue

Published Papers (5 papers)

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13 pages, 2732 KiB  
Article
The Influence of Oral Terbinafine on Gut Fungal Microbiome Composition and Microbial Translocation in People Living with HIV Treated for Onychomycosis
by Jing Ouyang, Jiangyu Yan, Xin Zhou, Stéphane Isnard, Shengquan Tang, Cecilia T. Costiniuk, Yaling Chen, Jean-Pierre Routy and Yaokai Chen
J. Fungi 2023, 9(10), 963; https://doi.org/10.3390/jof9100963 - 25 Sep 2023
Viewed by 3522
Abstract
People living with HIV (PLWH) display altered gut epithelium that allows for the translocation of microbial products, contributing to systemic immune activation. Although there are numerous studies which examine the gut bacterial microbiome in PLWH, few studies describing the fungal microbiome, or the [...] Read more.
People living with HIV (PLWH) display altered gut epithelium that allows for the translocation of microbial products, contributing to systemic immune activation. Although there are numerous studies which examine the gut bacterial microbiome in PLWH, few studies describing the fungal microbiome, or the mycobiome, have been reported. Like the gut bacterial microbiome, the fungal microbiome and its by-products play a role in maintaining the body’s homeostasis and modulating immune function. We conducted a prospective study to assess the effects of oral terbinafine, an antifungal agent widely used against onychomycosis, on gut permeability and microbiome composition in ART-treated PLWH (trial registration: ChiCTR2100043617). Twenty participants completed all follow-up visits. During terbinafine treatment, the levels of the intestinal fatty acid binding protein (I-FABP) significantly increased, and the levels of interleukin-6 (IL-6) significantly decreased, from baseline to week 12. Both markers subsequently returned to pre-treatment levels after terbinafine discontinuation. After terbinafine treatment, the abundance of fungi decreased significantly, while the abundance of the bacteria did not change. After terbinafine discontinuation, the abundance of fungi returned to the levels observed pre-treatment. Moreover, terbinafine treatment induced only minor changes in the composition of the gut bacterial and fungal microbiome. In summary, oral terbinafine decreases fungal microbiome abundance while only slightly influencing gut permeability and microbial translocation in ART-treated PLWH. This study’s findings should be validated in larger and more diverse studies of ART-treated PLWH; our estimates of effect size can be used to inform optimal sample sizes for future studies. Full article
(This article belongs to the Special Issue New Insights into Current Understanding of Host–Fungal Interactions)
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14 pages, 2675 KiB  
Article
Aspergillus fumigatus Supernatants Disrupt Bronchial Epithelial Monolayers: Potential Role for Enhanced Invasion in Cystic Fibrosis
by Katie Dunne, Emma Reece, Siobhán McClean, Sean Doyle, Thomas R. Rogers, Philip Murphy and Julie Renwick
J. Fungi 2023, 9(4), 490; https://doi.org/10.3390/jof9040490 - 19 Apr 2023
Cited by 2 | Viewed by 2071
Abstract
Aspergillus fumigatus is the most commonly isolated fungus in chronic lung diseases, with a prevalence of up to 60% in cystic fibrosis patients. Despite this, the impact of A. fumigatus colonisation on lung epithelia has not been thoroughly explored. We investigated the influence [...] Read more.
Aspergillus fumigatus is the most commonly isolated fungus in chronic lung diseases, with a prevalence of up to 60% in cystic fibrosis patients. Despite this, the impact of A. fumigatus colonisation on lung epithelia has not been thoroughly explored. We investigated the influence of A. fumigatus supernatants and the secondary metabolite, gliotoxin, on human bronchial epithelial cells (HBE) and CF bronchial epithelial (CFBE) cells. CFBE (F508del CFBE41o−) and HBE (16HBE14o−) trans-epithelial electrical resistance (TEER) was measured following exposure to A. fumigatus reference and clinical isolates, a gliotoxin-deficient mutant (ΔgliG) and pure gliotoxin. The impact on tight junction (TJ) proteins, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were determined by western blot analysis and confocal microscopy. A. fumigatus conidia and supernatants caused significant disruption to CFBE and HBE TJs within 24 h. Supernatants from later cultures (72 h) caused the greatest disruption while ΔgliG mutant supernatants caused no disruption to TJ integrity. The ZO-1 and JAM-A distribution in epithelial monolayers were altered by A. fumigatus supernatants but not by ΔgliG supernatants, suggesting that gliotoxin is involved in this process. The fact that ΔgliG conidia were still capable of disrupting epithelial monolayers indicates that direct cell–cell contact also plays a role, independently of gliotoxin production. Gliotoxin is capable of disrupting TJ integrity which has the potential to contribute to airway damage, and enhance microbial invasion and sensitisation in CF. Full article
(This article belongs to the Special Issue New Insights into Current Understanding of Host–Fungal Interactions)
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12 pages, 2010 KiB  
Article
Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
by Carolina Rodríguez-Echeverri, Beatriz L. Gómez and Ángel González
J. Fungi 2022, 8(10), 1108; https://doi.org/10.3390/jof8101108 - 20 Oct 2022
Cited by 4 | Viewed by 1842
Abstract
Hematopoietic stem cells (HSCs), a multipotent and self-renewing population responsible for the generation and maintenance of blood cells, have been the subject of numerous investigations due to their therapeutic potential. It has been shown that these cells are able to interact with pathogens [...] Read more.
Hematopoietic stem cells (HSCs), a multipotent and self-renewing population responsible for the generation and maintenance of blood cells, have been the subject of numerous investigations due to their therapeutic potential. It has been shown that these cells are able to interact with pathogens through the TLRs that they express on their surface, affecting the hematopoiesis process. However, the interaction between hematopoietic stem and progenitor cells (HSPC) with fungal pathogens such as Histoplasma capsulatum has not been studied. Therefore, the objective of the present study was to determine if the interaction of HSPCs with H. capsulatum yeasts affects the hematopoiesis, activation, or proliferation of these cells. The results indicate that HSPCs are able to adhere to and internalize H. capsulatum yeasts through a mechanism dependent on TLR2, TLR4, and Dectin-1; however, this process does not affect the survival of the fungus, and, on the contrary, such interaction induces a significant increase in the expression of IL-1β, IL-6, IL-10, IL-17, TNF-α, and TGF-β, as well as the immune mediators Arg-1 and iNOS. Moreover, H. capsulatum induces apoptosis and alters HSPC proliferation. These findings suggest that H. capsulatum directly modulates the immune response exerted by HPSC through PRRs, and this interaction could directly affect the process of hematopoiesis, a fact that could explain clinical manifestations such as anemia and pancytopenia in patients with severe histoplasmosis, especially in those with fungal spread to the bone marrow. Full article
(This article belongs to the Special Issue New Insights into Current Understanding of Host–Fungal Interactions)
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11 pages, 1032 KiB  
Article
The Effect of Antibiotics on the Infant Gut Fungal Microbiota
by Rebecka Ventin-Holmberg, Schahzad Saqib, Katri Korpela, Anne Nikkonen, Ville Peltola, Anne Salonen, Willem M. de Vos and Kaija-Leena Kolho
J. Fungi 2022, 8(4), 328; https://doi.org/10.3390/jof8040328 - 22 Mar 2022
Cited by 15 | Viewed by 8412
Abstract
Antibiotics are commonly used drugs in infants, causing disruptions in the developing gut microbiota with possible detrimental long-term effects such as chronic inflammatory diseases. The focus has been on bacteria, but research shows that fungi might have an important role as well. There [...] Read more.
Antibiotics are commonly used drugs in infants, causing disruptions in the developing gut microbiota with possible detrimental long-term effects such as chronic inflammatory diseases. The focus has been on bacteria, but research shows that fungi might have an important role as well. There are only a few studies on the infant gut fungal microbiota, the mycobiota, in relation to antibiotic treatment. Here, the aim was to investigate the impact of antibiotics on the infant gut mycobiota, and the interkingdom associations between bacteria and fungi. We had 37 antibiotic-naïve patients suffering from respiratory syncytial virus, of which 21 received one to four courses of antibiotics due to complications, and 16 remained antibiotic-naïve throughout the study. Fecal samples were collected before, during and after antibiotic treatment with a follow-up period of up to 9.5 months. The gut mycobiota was studied by Illumina MiSeq sequencing of the ITS1 region. We found that antibiotic use affected the gut mycobiota, most prominently seen as a higher relative abundance of Candida (p < 0.001), and a higher fungal diversity (p = 0.005–0.04) and richness (p = 0.03) in the antibiotic-treated infants compared to the antibiotic-naïve ones at multiple timepoints. This indicates that the gut mycobiota could contribute to the long-term consequences of antibiotic treatments. Full article
(This article belongs to the Special Issue New Insights into Current Understanding of Host–Fungal Interactions)
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9 pages, 1274 KiB  
Brief Report
Bile Acid Regulates Mononuclear Phagocytes and T Helper 17 Cells to Control Candida albicans in the Intestine
by Abhishek Datta, Juan F. Hernandez-Franco, Sungtae Park, Matthew R. Olson, Harm HogenEsch and Shankar Thangamani
J. Fungi 2022, 8(6), 610; https://doi.org/10.3390/jof8060610 - 7 Jun 2022
Cited by 6 | Viewed by 2843
Abstract
Invasive Candida albicans (CA) infections often arise from the intestine and cause life-threatening infections in immunocompromised individuals. The role of gut commensal microbiota, metabolites, and host factors in the regulation of CA colonization in the intestine is poorly understood. Previous findings [...] Read more.
Invasive Candida albicans (CA) infections often arise from the intestine and cause life-threatening infections in immunocompromised individuals. The role of gut commensal microbiota, metabolites, and host factors in the regulation of CA colonization in the intestine is poorly understood. Previous findings from our lab indicate that taurocholic acid (TCA), a major bile acid present in the intestine, promotes CA colonization and dissemination. Here, we report that oral administration of TCA to CA-infected mice significantly decreased the number of mononuclear phagocytes and CD4+ IL17A+ T helper 17 cells that play a critical role in controlling CA in the intestine. Collectively, our results indicate that TCA modulates mucosal innate and adaptive immune responses to promote CA colonization in the intestine. Full article
(This article belongs to the Special Issue New Insights into Current Understanding of Host–Fungal Interactions)
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