Journal of Fungi

Editorial

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3 pages, 193 KiB

Open AccessEditorial

Special Issue: Host Defense against Fungi

by Joseph M. Bliss

J. Fungi 2021, 7(12), 1054; https://doi.org/10.3390/jof7121054 - 9 Dec 2021

Viewed by 2079

Abstract

Pathogenic fungi represent a small subset of a markedly diverse kingdom of organisms [...] Full article

(This article belongs to the Special Issue Host Defense against Fungi)

Research

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14 pages, 825 KiB

Open AccessArticle

Clinical Characteristics and Outcomes of Fungal Keratitis in the United Kingdom 2011–2020: A 10-Year Study

by Darren Shu Jeng Ting, Mohamed Galal, Bina Kulkarni, Mohamed S. Elalfy, Damian Lake, Samer Hamada, Dalia G. Said and Harminder S. Dua

J. Fungi 2021, 7(11), 966; https://doi.org/10.3390/jof7110966 - 12 Nov 2021

Cited by 36 | Viewed by 4188

Abstract

Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) [...] Read more.

Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) that presented to Queen’s Medical Centre, Nottingham, and the Queen Victoria Hospital, East Grinstead, between 2011 and 2020 were included. We included 117 patients (n = 117 eyes) with FK in this study. The mean age was 59.0 ± 19.6 years (range, 4–92 years) and 51.3% of patients were female. Fifty-three fungal isolates were identified from 52 (44.4%) culture-positive cases, with Candida spp. (33, 62.3%), Fusarium spp. (9, 17.0%), and Aspergillus spp. (5, 9.4%) being the most common organisms. Ocular surface disease (60, 51.3%), prior corneal surgery (44, 37.6%), and systemic immunosuppression (42, 35.9%) were the three most common risk factors. Hospitalisation for intensive treatment was required for 95 (81.2%) patients, with a duration of 18.9 ± 16.3 days. Sixty-six (56.4%) patients required additional surgical interventions for eradicating the infection. Emergency therapeutic/tectonic keratoplasty was performed in 29 (24.8%) cases, though 13 (44.8%) of them failed at final follow-up. The final corrected-distance-visual-acuity (CDVA) was 1.67 ± 1.08 logMAR. Multivariable logistic regression analyses demonstrated increased age, large infiltrate size (>3 mm), and poor presenting CDVA (<1.0 logMAR) as significant negative predictive factors for poor visual outcome (CDVA of <1.0 logMAR) and poor corneal healing (>60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty; all p < 0.05). In conclusion, FK represents a difficult-to-treat ocular infection that often results in poor visual outcomes, with a high need for surgical interventions. Innovative treatment strategies are urgently required to tackle this unmet need. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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21 pages, 2167 KiB

Open AccessArticle

Mass Spectrometry-Based Proteomic and Immunoproteomic Analyses of the Candida albicans Hyphal Secretome Reveal Diagnostic Biomarker Candidates for Invasive Candidiasis

by Catarina Vaz, Aida Pitarch, Emilia Gómez-Molero, Ahinara Amador-García, Michael Weig, Oliver Bader, Lucía Monteoliva and Concha Gil

J. Fungi 2021, 7(7), 501; https://doi.org/10.3390/jof7070501 - 23 Jun 2021

Cited by 18 | Viewed by 3598

Abstract

Invasive candidiasis (IC) is associated with high morbidity and mortality in hospitalized patients if not diagnosed early. Long-term use of central venous catheters is a predisposing factor for IC. Hyphal forms of Candida albicans (the major etiological agent of IC) are related to [...] Read more.

Invasive candidiasis (IC) is associated with high morbidity and mortality in hospitalized patients if not diagnosed early. Long-term use of central venous catheters is a predisposing factor for IC. Hyphal forms of Candida albicans (the major etiological agent of IC) are related to invasion of host tissues. The secreted proteins of hyphae are involved in virulence, host interaction, immune response, and immune evasion. To identify IC diagnostic biomarker candidates, we characterized the C. albicans hyphal secretome by gel-free proteomic analysis, and further assessed the antibody-reactivity patterns to this subproteome in serum pools from 12 patients with non-catheter-associated IC (ncIC), 11 patients with catheter-associated IC (cIC), and 11 non-IC patients. We identified 301 secreted hyphal proteins stratified to stem from the extracellular region, cell wall, cell surface, or intracellular compartments. ncIC and cIC patients had higher antibody levels to the hyphal secretome than non-IC patients. Seven secreted hyphal proteins were identified to be immunogenic (Bgl2, Eno1, Pgk1, Glx3, Sap5, Pra1 and Tdh3). Antibody-reactivity patterns to Bgl2, Eno1, Pgk1 and Glx3 discriminated IC patients from non-IC patients, while those to Sap5, Pra1 and Tdh3 differentiated between cIC and non-IC patients. These proteins may be useful for development of future IC diagnostic tests. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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10 pages, 8298 KiB

Open AccessArticle

Neutrophil Cells Are Essential for The Efficacy of a Therapeutic Vaccine against Paracoccidioidomycosis

by Lucas dos Santos Dias, Leandro B. R. Silva, Joshua D. Nosanchuk and Carlos Pelleschi Taborda

J. Fungi 2021, 7(6), 416; https://doi.org/10.3390/jof7060416 - 26 May 2021

Cited by 4 | Viewed by 2924

Abstract

Paracoccidioidomycosis (PCM), caused by the Paracoccidioides species, is a systemic disease endemic in several Latin American countries, mainly in Brazil, Colombia, Argentina, and Venezuela. Current treatment approaches are challenging as they require prolonged durations of antifungal drugs that have potential toxicities, and despite [...] Read more.

Paracoccidioidomycosis (PCM), caused by the Paracoccidioides species, is a systemic disease endemic in several Latin American countries, mainly in Brazil, Colombia, Argentina, and Venezuela. Current treatment approaches are challenging as they require prolonged durations of antifungal drugs that have potential toxicities, and despite antifungals, relapses are common. Hence, new therapeutic approaches, such as vaccines, are being investigated. The therapeutic vaccine consisting of peptide P10 associated with lipid cationic DODAB (P10+DODAB) is effective in murine models of PCM. However, the specific immune mechanisms required for the protective response has not been fully elucidated. The present work aims at evaluating the participation of neutrophils in the immune response induced by P10+DODAB. We found that the vaccine reduced both the influx of pulmonary neutrophils and the fungal load in comparison to infected animals that did not receive this treatment. The parenchymal architecture of the lungs of P10+DODAB-treated animals was largely preserved with only a few granulomas present, and tissue cytokine analysis showed a Th1 cytokine profile with augmented levels of IL-12, IFN-γ and TNF-α, and low levels of IL-4. When neutrophils were depleted 24 h prior to each treatment, the effectiveness of the P10+DODAB vaccine was completely lost as the fungal burdens remained high and histological examination showed a marked inflammation and fungal dissemination with a dysregulated cytokine response. In conclusion, these findings indicate that neutrophils are vital to ensure the triggering of an effective immune response to P10+DODAB. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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18 pages, 3543 KiB

Open AccessArticle

Global Transcriptome Profiling Identified Transcription Factors, Biological Process, and Associated Pathways for Pre-Harvest Aflatoxin Contamination in Groundnut

by Pooja Soni, Arun K. Pandey, Spurthi N. Nayak, Manish K. Pandey, Priya Tolani, Sarita Pandey, Hari K. Sudini, Prasad Bajaj, Jake C. Fountain, Prashant Singam, Baozhu Guo and Rajeev K. Varshney

J. Fungi 2021, 7(6), 413; https://doi.org/10.3390/jof7060413 - 26 May 2021

Cited by 10 | Viewed by 4106

Abstract

Pre-harvest aflatoxin contamination (PAC) in groundnut is a serious quality concern globally, and drought stress before harvest further exacerbate its intensity, leading to the deterioration of produce quality. Understanding the host–pathogen interaction and identifying the candidate genes responsible for resistance to PAC will [...] Read more.

Pre-harvest aflatoxin contamination (PAC) in groundnut is a serious quality concern globally, and drought stress before harvest further exacerbate its intensity, leading to the deterioration of produce quality. Understanding the host–pathogen interaction and identifying the candidate genes responsible for resistance to PAC will provide insights into the defense mechanism of the groundnut. In this context, about 971.63 million reads have been generated from 16 RNA samples under controlled and Aspergillus flavus infected conditions, from one susceptible and seven resistant genotypes. The RNA-seq analysis identified 45,336 genome-wide transcripts under control and infected conditions. This study identified 57 transcription factor (TF) families with major contributions from 6570 genes coding for bHLH (719), MYB-related (479), NAC (437), FAR1 family protein (320), and a few other families. In the host (groundnut), defense-related genes such as senescence-associated proteins, resveratrol synthase, seed linoleate, pathogenesis-related proteins, peroxidases, glutathione-S-transferases, chalcone synthase, ABA-responsive gene, and chitinases were found to be differentially expressed among resistant genotypes as compared to susceptible genotypes. This study also indicated the vital role of ABA-responsive ABR17, which co-regulates the genes of ABA responsive elements during drought stress, while providing resistance against A. flavus infection. It belongs to the PR-10 class and is also present in several plant–pathogen interactions. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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18 pages, 1829 KiB

Open AccessArticle

Candida albicans/Macrophage Biointerface on Human and Porcine Decellularized Adipose Matrices

by Mónica Cicuéndez, Laura Casarrubios, María José Feito, Iratxe Madarieta, Nerea Garcia-Urkia, Olatz Murua, Beatriz Olalde, Nerea Briz, Rosalía Diez-Orejas and María Teresa Portolés

J. Fungi 2021, 7(5), 392; https://doi.org/10.3390/jof7050392 - 17 May 2021

Cited by 4 | Viewed by 3083

Abstract

Macrophages, cells effective in sensing, internalizing and killing Candida albicans, are intertwined with the extracellular matrix (ECM) through different signals, which include the release of specific cytokines. Due to the importance of these interactions, the employment of in vitro models mimicking a [...] Read more.

Macrophages, cells effective in sensing, internalizing and killing Candida albicans, are intertwined with the extracellular matrix (ECM) through different signals, which include the release of specific cytokines. Due to the importance of these interactions, the employment of in vitro models mimicking a fungal infection scenario is essential to evaluate the ECM effects on the macrophage response. In this work, we have analyzed the effects of human and porcine decellularized adipose matrices (DAMs), obtained by either enzymatic or organic solvent treatment, on the macrophage/Candida albicans interface. The present study has allowed us to detect differences on the activation of macrophages cultured on either human- or porcine-derived DAMs, evidencing changes in the macrophage actin cytoskeleton, such as distinct F-actin-rich membrane structures to surround the pathogen. The macrophage morphological changes observed on these four DAMs are key to understand the defense capability of these cells against this fungal pathogen. This work has contributed to the knowledge of the influence that the extracellular matrix and its components can exert on macrophage metabolism, immunocompetence and capacity to respond to the microenvironment in a possible infection scenario. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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18 pages, 3966 KiB

Open AccessArticle

Identification of the Ricin-B-Lectin LdRBLk in the Colorado Potato Beetle and an Analysis of Its Expression in Response to Fungal Infections

by Ulyana N. Rotskaya, Vadim Yu. Kryukov, Elena Kosman, Maksim Tyurin and Viktor V. Glupov

J. Fungi 2021, 7(5), 364; https://doi.org/10.3390/jof7050364 - 6 May 2021

Cited by 6 | Viewed by 2950

Abstract

Ricin-B-lectins (RBLs) have been identified in many groups of organisms, including coleopterans insects, particularly the Colorado potato beetle Leptinotarsa decemlineata (LdRBLs). We hypothesized that one of these LdRBLs (LdRBLk) may be involved in the immune response to fungal infections. We performed a theoretical [...] Read more.

Ricin-B-lectins (RBLs) have been identified in many groups of organisms, including coleopterans insects, particularly the Colorado potato beetle Leptinotarsa decemlineata (LdRBLs). We hypothesized that one of these LdRBLs (LdRBLk) may be involved in the immune response to fungal infections. We performed a theoretical analysis of the structure of this protein. Additionally, the expression levels of the LdRBlk gene were measured in L. decemlineata in response to infections with the fungi Metarhizium robertsii and Beauveria bassiana. The expression levels of LdRBlk in the L. decemlineata cuticle and fat body were increased in response to both infections. The induction of LdRBlk expression was dependent on the susceptibility of larvae to the fungi. Upregulation of the LdRBlk gene was also observed in response to other stresses, particularly thermal burns. Elevation of LdRBlk expression was frequently observed to be correlated with the expression of the antimicrobial peptide attacin but was not correlated with hsp90 regulation. Commercially available β-lectin of ricin from Ricinuscommunis was observed to inhibit the germination of conidia of the fungi. We suggest that LdRBLk is involved in antifungal immune responses in the Colorado potato beetle, either exerting fungicidal properties directly or acting as a modulator of the immune response. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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13 pages, 2316 KiB

Open AccessArticle

Dexamethasone Creates a Suppressive Microenvironment and Promotes Aspergillus fumigatus Invasion in a Human 3D Epithelial/Immune Respiratory Model

by Maureen K. Luvanda, Wilfried Posch, Asma Noureen, Eliott Lafon, Viktoria Zaderer, Cornelia Lass-Flörl and Doris Wilflingseder

J. Fungi 2021, 7(3), 221; https://doi.org/10.3390/jof7030221 - 18 Mar 2021

Cited by 6 | Viewed by 4496

Abstract

Lung immunity and susceptibility to infections is subject to interactions between the epithelial layer and immune cells residing in the pulmonary space. Aspergillus (A.) fumigatus, the most prevalent pathogenic fungus, affects both upper and lower respiratory tracts of immunocompromised hosts. Several reports [...] Read more.

Lung immunity and susceptibility to infections is subject to interactions between the epithelial layer and immune cells residing in the pulmonary space. Aspergillus (A.) fumigatus, the most prevalent pathogenic fungus, affects both upper and lower respiratory tracts of immunocompromised hosts. Several reports implicate corticosteroids as a major risk factor due to their anti-inflammatory and immunosuppressive effects, which are exacerbated by long-term treatment regimens. Here we demonstrate for the first time the influence of dexamethasone when it comes to germination and hyphae formation of A. fumigatus in the presence of macrophages within a highly differentiated air–liquid interphase (ALI) epithelial/immune lung model. We illustrate suppressed mucus production within the highly differentiated 3D respiratory model as well as significantly decreased cilia beat frequencies by dexamethasone treatment. This goes along with corticosteroid-mediated macrophage M2 polarization within the epithelial/immune microenvironment. Therefore, we here showed that corticosteroids promote enhanced fungal growth and invasion A. fumigatus by creating a suppressive environment affecting both epithelial as well as immune cells. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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15 pages, 269 KiB

Open AccessArticle

Atopic Dermatitis and Sensitisation to Molecular Components of Alternaria, Cladosporium, Penicillium, Aspergillus, and Malassezia—Results of Allergy Explorer ALEX 2

by Jarmila Celakovska, Radka Vankova, Josef Bukac, Eva Cermakova, Ctirad Andrys and Jan Krejsek

J. Fungi 2021, 7(3), 183; https://doi.org/10.3390/jof7030183 - 4 Mar 2021

Cited by 18 | Viewed by 3780

Abstract

Progress in laboratory diagnostics of IgE-mediated allergies is being made through the use of component-resolved diagnosis. The aim of our study is to analyze the sensitization profile to allergen reagents in patients suffering from atopic dermatitis with the use of the ALEX 2–Allergy [...] Read more.

Progress in laboratory diagnostics of IgE-mediated allergies is being made through the use of component-resolved diagnosis. The aim of our study is to analyze the sensitization profile to allergen reagents in patients suffering from atopic dermatitis with the use of the ALEX 2–Allergy Explorer and especially to show the sensitization to molecular components of molds and yeast. The complete dermatological and allergological examination including the examination of the sensitization to allergen reagents with Allergy Explorer ALEX 2 testing was performed. The relation between the sensitization to molecular components of molds and yeast and the severity of atopic dermatitis, and the occurrence of bronchial asthma and allergic rhinitis was evaluated. Altogether, 100 atopic dermatitis patients were examined—48 men and 52 women, with an average age of 40.9 years. The sensitization to Mala s 6, Mala s 11, Sac c, Asp f 6, Cla h and Cla h 8 correlates to the severity of atopic dermatitis. The sensitization to Sac c, Alt a 6, Cla h, Cla h 8 was observed significantly more frequently in patients suffering from bronchial asthma to Mala s 6 in patients suffering from allergic rhinitis. In patients with severe form of atopic dermatitis (AD), a very high level of specific IgE was recorded to Mala s 11 (in 36%) and to Asp f 6 (in 12%). Full article

(This article belongs to the Special Issue Host Defense against Fungi)

23 pages, 10778 KiB

Open AccessArticle

Transcriptome Analysis Identified Coordinated Control of Key Pathways Regulating Cellular Physiology and Metabolism upon Aspergillus flavus Infection Resulting in Reduced Aflatoxin Production in Groundnut

by Pooja Soni, Spurthi N. Nayak, Rakesh Kumar, Manish K. Pandey, Namita Singh, Hari K. Sudini, Prasad Bajaj, Jake C. Fountain, Prashant Singam, Yanbin Hong, Xiaoping Chen, Weijian Zhuang, Boshou Liao, Baozhu Guo and Rajeev K. Varshney

J. Fungi 2020, 6(4), 370; https://doi.org/10.3390/jof6040370 - 16 Dec 2020

Cited by 15 | Viewed by 4778

Abstract

Aflatoxin-affected groundnut or peanut presents a major global health issue to both commercial and subsistence farming. Therefore, understanding the genetic and molecular mechanisms associated with resistance to aflatoxin production during host–pathogen interactions is crucial for breeding groundnut cultivars with minimal level of aflatoxin [...] Read more.

Aflatoxin-affected groundnut or peanut presents a major global health issue to both commercial and subsistence farming. Therefore, understanding the genetic and molecular mechanisms associated with resistance to aflatoxin production during host–pathogen interactions is crucial for breeding groundnut cultivars with minimal level of aflatoxin contamination. Here, we performed gene expression profiling to better understand the mechanisms involved in reduction and prevention of aflatoxin contamination resulting from Aspergillus flavus infection in groundnut seeds. RNA sequencing (RNA-Seq) of 16 samples from different time points during infection (24 h, 48 h, 72 h and the 7th day after inoculation) in U 4-7-5 (resistant) and JL 24 (susceptible) genotypes yielded 840.5 million raw reads with an average of 52.5 million reads per sample. A total of 1779 unique differentially expressed genes (DEGs) were identified. Furthermore, comprehensive analysis revealed several pathways, such as disease resistance, hormone biosynthetic signaling, flavonoid biosynthesis, reactive oxygen species (ROS) detoxifying, cell wall metabolism and catabolizing and seed germination. We also detected several highly upregulated transcription factors, such as ARF, DBB, MYB, NAC and C2H2 in the resistant genotype in comparison to the susceptible genotype after inoculation. Moreover, RNA-Seq analysis suggested the occurrence of coordinated control of key pathways controlling cellular physiology and metabolism upon A. flavus infection, resulting in reduced aflatoxin production. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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14 pages, 1970 KiB

Open AccessArticle

Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (pANCA) Impair Neutrophil Candidacidal Activity and Are Increased in the Cellular Fraction of Vaginal Samples from Women with Vulvovaginal Candidiasis

by Andrea Ardizzoni, Arianna Sala, Bruna Colombari, Lavinia Beatrice Giva, Claudio Cermelli, Samuele Peppoloni, Anna Vecchiarelli, Elena Roselletti, Elisabetta Blasi, Robert T. Wheeler and Eva Pericolini

J. Fungi 2020, 6(4), 225; https://doi.org/10.3390/jof6040225 - 16 Oct 2020

Cited by 11 | Viewed by 3274

Abstract

Vulvovaginal candidiasis (VVC) is primarily caused by Candida albicans and affects 75% of childbearing age women. Although C. albicans can colonize asymptomatically, disease is associated with an increased Candida burden, a loss of epithelial tolerance and a breakdown in vaginal microbiota homeostasis. VVC [...] Read more.

Vulvovaginal candidiasis (VVC) is primarily caused by Candida albicans and affects 75% of childbearing age women. Although C. albicans can colonize asymptomatically, disease is associated with an increased Candida burden, a loss of epithelial tolerance and a breakdown in vaginal microbiota homeostasis. VVC symptoms have been ascribed to a powerful inflammatory response associated with the infiltration of non-protective neutrophils (PMN). Here, we compared the immunological characteristics of vaginal fluids and cellular protein extracts obtained from 28 VVC women and from 23 healthy women colonized by Candida spp. We measured the levels of antibodies against fungal antigens and human autoantigens (anti-Saccharomyces cerevisiae antibodies (ASCA), C. albicans germ tube antibodies (CAGTAs) and perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)), in addition to other immunological markers. Our results show that the pANCA levels detected in the cellular protein extracts from the vaginal fluids of symptomatic women were significantly higher than those obtained from healthy colonized women. Consistent with a potential physiologically relevant role for this pANCA, we found that specific anti-myeloperoxidase antibodies could completely neutralize the ex vivo killing capacity of polymorphonuclear cells. Collectively, this preliminary study suggests for the first time that pANCA are found in the pathogenic vaginal environment and can promptly impair neutrophil function against Candida, potentially preventing a protective response. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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Review

Jump to: Editorial, Research

26 pages, 4436 KiB

Open AccessReview

Oral Candidosis: Pathophysiology and Best Practice for Diagnosis, Classification, and Successful Management

by Shin-Yu Lu

J. Fungi 2021, 7(7), 555; https://doi.org/10.3390/jof7070555 - 13 Jul 2021

Cited by 43 | Viewed by 20906

Abstract

Oral candidosis is the most common fungal infection that frequently occurs in patients debilitated by other diseases or conditions. No candidosis happens without a cause; hence oral candidosis has been branded as a disease of the diseased. Prior research has identified oral candidosis [...] Read more.

Oral candidosis is the most common fungal infection that frequently occurs in patients debilitated by other diseases or conditions. No candidosis happens without a cause; hence oral candidosis has been branded as a disease of the diseased. Prior research has identified oral candidosis as a mark of systemic diseases, such as hematinic deficiency, diabetes mellitus, leukopenia, HIV/AIDS, malignancies, and carbohydrate-rich diet, drugs, or immunosuppressive conditions. An array of interaction between Candida and the host is dynamic and complex. Candida exhibits multifaceted strategies for growth, proliferation, evasion of host defenses, and survival within the host to induce fungal infection. Oral candidosis presents a variety of clinical forms, including pseudomembranous candidosis, erythematous candidosis, angular cheilitis, median rhomboid glossitis, cheilocandidosis, juxtavermillion candidosis, mucocutaneous candidosis, hyperplastic candidosis, oropharyngeal candidosis, and rare suppurative candidosis. The prognosis is usually favorable, but treatment failure or recurrence is common due to either incorrect diagnosis, missing other pathology, inability to address underlying risk factors, or inaccurate prescription of antifungal agents. In immunocompromised patients, oropharyngeal candidosis can spread to the bloodstream or upper gastrointestinal tract, leading to potentially lethal systemic candidosis. This review therefore describes oral candidosis with regard to its pathophysiology and best practice for diagnosis, practical classification, and successful management. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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18 pages, 2457 KiB

Open AccessReview

Immune Cell Degranulation in Fungal Host Defence

by Adley CH. Mok, Christopher H. Mody and Shu Shun Li

J. Fungi 2021, 7(6), 484; https://doi.org/10.3390/jof7060484 - 16 Jun 2021

Cited by 7 | Viewed by 3738

Abstract

Humans have developed complex immune systems that defend against invading microbes, including fungal pathogens. Many highly specialized cells of the immune system share the ability to store antimicrobial compounds in membrane bound organelles that can be immediately deployed to eradicate or inhibit growth [...] Read more.

Humans have developed complex immune systems that defend against invading microbes, including fungal pathogens. Many highly specialized cells of the immune system share the ability to store antimicrobial compounds in membrane bound organelles that can be immediately deployed to eradicate or inhibit growth of invading pathogens. These membrane-bound organelles consist of secretory vesicles or granules, which move to the surface of the cell, where they fuse with the plasma membrane to release their contents in the process of degranulation. Lymphocytes, macrophages, neutrophils, mast cells, eosinophils, and basophils all degranulate in fungal host defence. While anti-microbial secretory vesicles are shared among different immune cell types, information about each cell type has emerged independently leading to an uncoordinated and confusing classification of granules and incomplete description of the mechanism by which they are deployed. While there are important differences, there are many similarities in granule morphology, granule content, stimulus for degranulation, granule trafficking, and release of granules against fungal pathogens. In this review, we describe the similarities and differences in an attempt to translate knowledge from one immune cell to another that may facilitate further studies in the context of fungal host defence. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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23 pages, 800 KiB

Open AccessReview

Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art

by Georgios Karavalakis, Evangelia Yannaki and Anastasia Papadopoulou

J. Fungi 2021, 7(6), 451; https://doi.org/10.3390/jof7060451 - 6 Jun 2021

Cited by 9 | Viewed by 3855

Abstract

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated [...] Read more.

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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13 pages, 519 KiB

Open AccessReview

Radionuclide Imaging of Fungal Infections and Correlation with the Host Defense Response

by Alfred O. Ankrah, Mike M. Sathekge, Rudi A. J. O. Dierckx and Andor W. J. M. Glaudemans

J. Fungi 2021, 7(6), 407; https://doi.org/10.3390/jof7060407 - 22 May 2021

Cited by 8 | Viewed by 3046

Abstract

The human response to invading fungi includes a series of events that detect, kill, or clear the fungi. If the metabolic host response is unable to eliminate the fungi, an infection ensues. Some of the host response’s metabolic events to fungi can be [...] Read more.

The human response to invading fungi includes a series of events that detect, kill, or clear the fungi. If the metabolic host response is unable to eliminate the fungi, an infection ensues. Some of the host response’s metabolic events to fungi can be imaged with molecules labelled with radionuclides. Several important clinical applications have been found with radiolabelled biomolecules of inflammation. ¹⁸F-fluorodeoxyglucose is the tracer that has been most widely investigated in the host defence of fungi. This tracer has added value in the early detection of infection, in staging and visualising dissemination of infection, and in monitoring antifungal treatment. Radiolabelled antimicrobial peptides showed promising results, but large prospective studies in fungal infection are lacking. Other tracers have also been used in imaging events of the host response, such as the migration of white blood cells at sites of infection, nutritional immunity in iron metabolism, and radiolabelled monoclonal antibodies. Many tracers are still at the preclinical stage. Some tracers require further studies before translation into clinical use. The application of therapeutic radionuclides offers a very promising clinical application of these tracers in managing drug-resistant fungi. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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29 pages, 1746 KiB

Open AccessReview

Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

by Marhiah C. Montoya, Paul M. Magwene and John R. Perfect

J. Fungi 2021, 7(4), 260; https://doi.org/10.3390/jof7040260 - 30 Mar 2021

Cited by 49 | Viewed by 8712

Abstract

The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central nervous system disease. Patients [...] Read more.

The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central nervous system disease. Patients with cryptococcosis can display a variety of symptoms on a spectrum of severity because of the interaction between yeast and host. The bulk of our knowledge regarding Cryptococcus and the mechanisms of disease stem from in vitro experiments and in vivo animal models that make a fair attempt, but do not recapitulate the conditions inside the human host. To better understand the dynamics of initiation and progression in cryptococcal disease, it is important to study the genetic and phenotypic differences in the context of human infection to identify the human and fungal risk factors that contribute to pathogenesis and poor clinical outcomes. In this review, we summarize the current understanding of the different clinical presentations and health outcomes that are associated with pathogenicity and virulence of cryptococcal strains with respect to specific genotypes and phenotypes. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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16 pages, 1072 KiB

Open AccessReview

Complex and Controversial Roles of Eicosanoids in Fungal Pathogenesis

by Susana Ruiz Mendoza, Daniel Zamith-Miranda, Tamás Takács, Attila Gacser, Joshua D. Nosanchuk and Allan J. Guimarães

J. Fungi 2021, 7(4), 254; https://doi.org/10.3390/jof7040254 - 28 Mar 2021

Cited by 13 | Viewed by 5246

Abstract

The prevalence of fungal infections has increased in immunocompromised patients, leading to millions of deaths annually. Arachidonic acid (AA) metabolites, such as eicosanoids, play important roles in regulating innate and adaptative immune function, particularly since they can function as virulence factors enhancing fungal [...] Read more.

The prevalence of fungal infections has increased in immunocompromised patients, leading to millions of deaths annually. Arachidonic acid (AA) metabolites, such as eicosanoids, play important roles in regulating innate and adaptative immune function, particularly since they can function as virulence factors enhancing fungal colonization and are produced by mammalian and lower eukaryotes, such as yeasts and other fungi (Candida albicans, Histoplasma capsulatum and Cryptococcus neoformans). C. albicans produces prostaglandins (PG), Leukotrienes (LT) and Resolvins (Rvs), whereas the first two have been well documented in Cryptococcus sp. and H. capsulatum. In this review, we cover the eicosanoids produced by the host and fungi during fungal infections. These fungal-derived PGs have immunomodulatory functions analogous to their mammalian counterparts. Prostaglandin E₂ (PGE₂) protects C. albicans and C. parapsilosis cells from the phagocytic and killing activity of macrophages. H. capsulatum PGs augment the fungal burden and host mortality rates in histoplasmosis. However, PGD₂ potentiates the effects and production of LTB₄, which is a very potent neutrophil chemoattractant that enhances host responses. Altogether, these data suggest that eicosanoids, mainly PGE₂, may serve as a new potential target to combat diverse fungal infections. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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15 pages, 2066 KiB

Open AccessReview

Fungal-Induced Programmed Cell Death

by Thomas J. Williams, Luis E. Gonzales-Huerta and Darius Armstrong-James

J. Fungi 2021, 7(3), 231; https://doi.org/10.3390/jof7030231 - 20 Mar 2021

Cited by 16 | Viewed by 4981

Abstract

Fungal infections are a cause of morbidity in humans, and despite the availability of a range of antifungal treatments, the mortality rate remains unacceptably high. Although our knowledge of the interactions between pathogenic fungi and the host continues to grow, further research is [...] Read more.

Fungal infections are a cause of morbidity in humans, and despite the availability of a range of antifungal treatments, the mortality rate remains unacceptably high. Although our knowledge of the interactions between pathogenic fungi and the host continues to grow, further research is still required to fully understand the mechanism underpinning fungal pathogenicity, which may provide new insights for the treatment of fungal disease. There is great interest regarding how microbes induce programmed cell death and what this means in terms of the immune response and resolution of infection as well as microbe-specific mechanisms that influence cell death pathways to aid in their survival and continued infection. Here, we discuss how programmed cell death is induced by fungi that commonly cause opportunistic infections, including Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, the role of programmed cell death in fungal immunity, and how fungi manipulate these pathways. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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9 pages, 289 KiB

Open AccessReview

Cryptococcus gattii in Patients with Lymphoid Neoplasms: An Illustration of Evolutive Host–Fungus Interactions

by Olivier Paccoud, Marie-Elisabeth Bougnoux, Marie Desnos-Ollivier, Bruno Varet, Olivier Lortholary and Fanny Lanternier

J. Fungi 2021, 7(3), 212; https://doi.org/10.3390/jof7030212 - 16 Mar 2021

Cited by 7 | Viewed by 2695

Abstract

Recent outbreaks of Cryptococcus gattii (CG) infections in North America have sparked renewed interest in the pathogenic potential of CG, and have underscored notable differences with Cryptococcus neoformans in terms of geographic distribution, pathogen virulence, and host susceptibility. While cases of CG are [...] Read more.

Recent outbreaks of Cryptococcus gattii (CG) infections in North America have sparked renewed interest in the pathogenic potential of CG, and have underscored notable differences with Cryptococcus neoformans in terms of geographic distribution, pathogen virulence, and host susceptibility. While cases of CG are increasingly reported in patients with a wide variety of underlying conditions, only very few have been reported in patients with lymphoid neoplasms. Herein, we report a case of autochthonous CG meningitis in a patient receiving ibrutinib for chronic lymphocytic leukemia in France, and review available data on the clinical epidemiology of CG infections in patients with lymphoid neoplasms. We also summarise recent data on the host responses to CG infection, as well as the potential management pitfalls associated with its treatment in the haematological setting. The clinical epidemiology, clinical presentation, and course of disease during infections caused by CG involve complex interactions between environmental exposure to CG, infecting genotype, pathogen virulence factors, host susceptibility, and host immune responses. Future treatment guidelines should address the challenges associated with the management of antifungal treatments in the onco-haematological setting and the potential drug-drug interactions. Full article

(This article belongs to the Special Issue Host Defense against Fungi)

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