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Innate Immunity in Fungal Infections
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Innate Immunity in Fungal Infections

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 2020) | Viewed by 50143

Special Issue Editors

Prof. Dr. Constantin Urban

E-Mail Website
Guest Editor
Department of Clinical Microbiology, Umea University, Umea, Sweden
Interests: fungal infection; Candida albicans; antimicrobials; innate immunity; clinical immunology; cell biology
Prof. Dr. Fanny Lanternier

E-Mail Website
Guest Editor
1. Department of Infectious and Tropical Diseases, Université de Paris, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France
2. Institut Pasteur, CNRMA, Unité de Mycologie Moléculaire, CNRS, Paris, France
Interests: aspergillosis; mucormycosis; scedosporiosis; primary immunodeficiency; host genetics of fungal infection

Special Issue Information

Dear Colleagues,

Species of the fungal kingdom, from whose entire diversity today only a small fraction of representatives is known, comprise a crucial part of earth’s ecosystems. 

Although only a small proportion of microbial fungal organisms were able to adapt to physiologic temperatures of endothermic hosts, this proportion is responsible for increasing infections in humans and animals, imposing a significant burden on health care and economy. Superficial mycoses in humans affecting mucosal, skin and nails are very frequent, giving rise to an estimated number of more than 2 billion annual infections worldwide. However, our innate immune system limits these infections and forms an effective barrier preventing deep-seated fungal infections. Furthermore, innate (antifungal) immunity restricts prevalent fungal organisms which are either part of our normal flora or are ubiquitous in nature to harmless encounters. However, when this important barrier is breached in immunocompromised individuals, invasive and life-threatening infections with fungal organisms occur.

The number of hospitalized patients with acquired immunosuppression inherited or acquired immunodeficiency due to a primary disease or immunosuppressive therapy have been steadily increasing in recent decades. This increase has served as seed for an increasing number of severe infections with fungal pathogens, mainly of the genera Candida, Aspergillus, and Cryptococcus; however, infections with new species from new genera are emerging, such as mucormycoses. Moreover apparently immunocompetent patients developing fungal infections are identified with genetic suseptibility leading too the identification of new primary immunodefiiciency and better knowledge of antifungal immune response. Although antifungal drugs exist, the mortality of severe mycoses remains unacceptably high, exceeding 1.4 million deaths each year on the global scale. In regard to this clinical challenge, new therapy options and improved, rapid diagnostic tools are urgently needed. This, however, requires a detailed understanding of the molecular and cellular basis of innate antifungal immunity, which to date is only beginning to unfold. This Special Issue aims to gather innovative original research articles and stat-of-the-art reviews in the field of “Innate Immunity in Fungal Infections”.

Prof. Dr. Constantin F. Urban
Prof. Dr. Fanny Lanternier
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 defense against fungi
  • Fungal host interactions
  • Fungal infections
  • Primary immune deficiency
  • Innate immunity
  • Candida
  • Aspergillus
  • Cryptococcus

Published Papers (5 papers)

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Research

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17 pages, 31126 KiB  
Article
The Role of RodA-Conserved Cysteine Residues in the Aspergillus fumigatus Conidial Surface Organization
by Isabel Valsecchi, Emmanuel Stephen-Victor, Sarah Sze Wah Wong, Anupama Karnam, Margaret Sunde, J. Iñaki Guijarro, Borja Rodríguez de Francisco, Thomas Krüger, Olaf Kniemeyer, Gordon D. Brown, Janet A. Willment, Jean-Paul Latgé, Axel A. Brakhage, Jagadeesh Bayry and Vishukumar Aimanianda
J. Fungi 2020, 6(3), 151; https://doi.org/10.3390/jof6030151 - 26 Aug 2020
Cited by 8 | Viewed by 3596
Abstract
Immune inertness of Aspergillusfumigatus conidia is attributed to its surface rodlet-layer made up of RodAp, characterized by eight conserved cysteine residues forming four disulfide bonds. Earlier, we showed that the conserved cysteine residue point (ccrp) mutations result in conidia devoid of the [...] Read more.
Immune inertness of Aspergillusfumigatus conidia is attributed to its surface rodlet-layer made up of RodAp, characterized by eight conserved cysteine residues forming four disulfide bonds. Earlier, we showed that the conserved cysteine residue point (ccrp) mutations result in conidia devoid of the rodlet layer. Here, we extended our study comparing the surface organization and immunoreactivity of conidia carrying ccrp-mutations with the RODA deletion mutant (∆rodA). Western blot analysis using anti-RodAp antibodies indicated the absence of RodAp in the cytoplasm of ccrp-mutant conidia. Immunolabeling revealed differential reactivity to conidial surface glucans, the ccrp-mutant conidia preferentially binding to α-(1,3)-glucan, ∆rodA conidia selectively bound to β-(1,3)-glucan; the parental strain conidia showed negative labeling. However, permeability of ccrp-mutants and ∆rodA was similar to the parental strain conidia. Proteomic analyses of the conidial surface exposed proteins of the ccrp-mutants showed more similarities with the parental strain, but were significantly different from the ∆rodA. Ccrp-mutant conidia were less immunostimulatory compared to ∆rodA conidia. Our data suggest that (i) the conserved cysteine residues are essential for the trafficking of RodAp and the organization of the rodlet layer on the conidial surface, and (ii) targeted point mutation could be an alternative approach to study the role of fungal cell-wall genes in host–fungal interaction. Full article
(This article belongs to the Special Issue Innate Immunity in Fungal Infections)
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15 pages, 2341 KiB  
Article
Antifungal Activity of Antimicrobial Peptides and Proteins against Aspergillus fumigatus
by Eloise Ballard, Raif Yucel, Willem J. G. Melchers, Alistair J. P. Brown, Paul E. Verweij and Adilia Warris
J. Fungi 2020, 6(2), 65; https://doi.org/10.3390/jof6020065 - 18 May 2020
Cited by 17 | Viewed by 4914
Abstract
Antimicrobial peptides and proteins (AMPs) provide an important line of defence against invading microorganisms. However, the activity of AMPs against the human fungal pathogen Aspergillus fumigatus remains poorly understood. Therefore, the aim of this study was to characterise the anti-Aspergillus activity of [...] Read more.
Antimicrobial peptides and proteins (AMPs) provide an important line of defence against invading microorganisms. However, the activity of AMPs against the human fungal pathogen Aspergillus fumigatus remains poorly understood. Therefore, the aim of this study was to characterise the anti-Aspergillus activity of specific human AMPs, and to determine whether A. fumigatus can possess resistance to specific AMPs, as a result of in-host adaptation. AMPs were tested against a wide range of clinical isolates of various origins (including cystic fibrosis patients, as well as patients with chronic and acute aspergillosis). We also tested a series of isogenic A. fumigatus isolates obtained from a single patient over a period of 2 years. A range of environmental isolates, obtained from soil in Scotland, was also included. Firstly, the activity of specific peptides was assessed against hyphae using a measure of fungal metabolic activity. Secondly, the activity of specific peptides was assessed against germinating conidia, using imaging flow cytometry as a measure of hyphal growth. We showed that lysozyme and histones inhibited hyphal metabolic activity in all the A. fumigatus isolates tested in a dose-dependent fashion. In addition, imaging flow cytometry revealed that histones, β-defensin-1 and lactoferrin inhibited the germination of A. fumigatus conidia. Full article
(This article belongs to the Special Issue Innate Immunity in Fungal Infections)
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Review

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12 pages, 2296 KiB  
Review
Urine Sediment Findings and the Immune Response to Pathologies in Fungal Urinary Tract Infections Caused by Candida spp.
by José Antonio Tesser Poloni and Liane Nanci Rotta
J. Fungi 2020, 6(4), 245; https://doi.org/10.3390/jof6040245 - 23 Oct 2020
Cited by 9 | Viewed by 30063
Abstract
Fungi are pathogenic agents that can also cause disseminated infections involving the kidneys. Besides Candida, other agents like Cryptococcus spp. can cause urinary tract infection (UTI), as well as other non-yeast fungi, especially among immunocompromised patients. The detection and identification of fungi [...] Read more.
Fungi are pathogenic agents that can also cause disseminated infections involving the kidneys. Besides Candida, other agents like Cryptococcus spp. can cause urinary tract infection (UTI), as well as other non-yeast fungi, especially among immunocompromised patients. The detection and identification of fungi in urine samples (by microscopy and culture) plays an essential role in the diagnosis of fungal UTI. However, variable cutoff definitions and unreliable culture techniques may skew analysis of the incidence and outcome of candiduria. The sediment analysis plays a key role in the identification of fungal UTI because both yeasts and pseudohyphae are easily identified and can be used as a clinical sign of fungal UTI but should not be overinterpreted. Indeed, urine markers of the immune response (leukocytes), urine barriers of tissue protection (epithelial cells), and urine markers of kidney disease (urinary casts) can be found in urine samples. This work explores the manifestations associated with the fungal UTI from the urinalysis perspective, namely the urinary findings and clinical picture of patients with fungal UTI caused by Candida spp., aspects associated with the immune response, and the future perspectives of urinalysis in the diagnosis of this clinical condition. Full article
(This article belongs to the Special Issue Innate Immunity in Fungal Infections)
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14 pages, 762 KiB  
Review
The Diverse Roles of Monocytes in Cryptococcosis
by Man Shun Fu and Rebecca A. Drummond
J. Fungi 2020, 6(3), 111; https://doi.org/10.3390/jof6030111 - 16 Jul 2020
Cited by 4 | Viewed by 8156
Abstract
Monocytes are considered to play a central role in the pathogenesis of Cryptococcus neoformans infection. Monocytes and monocyte-derived macrophages and dendritic cells are key components for the control of infection, but paradoxically they can also contribute to detrimental host responses and may even [...] Read more.
Monocytes are considered to play a central role in the pathogenesis of Cryptococcus neoformans infection. Monocytes and monocyte-derived macrophages and dendritic cells are key components for the control of infection, but paradoxically they can also contribute to detrimental host responses and may even support fungal proliferation and dissemination. Simultaneously, the C. neoformans polysaccharide capsule can impair the functions of monocytes. Although monocytes are often seen as simple precursor cells, they also function as independent immune effector cells. In this review, we summarize these monocyte-specific functions during cryptococcal infection and the influence of C. neoformans on monocyte responses. We also cover the most recent findings on the functional and phenotypic heterogeneity of monocytes and discuss how new advanced technologies provide a platform to address outstanding questions in the field. Full article
(This article belongs to the Special Issue Innate Immunity in Fungal Infections)
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Other

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7 pages, 1215 KiB  
Case Report
Functional Defect of Neutrophils Causing Dermatophytosis: Case Report
by Rosemeire N. Constantino-Silva, Sandro F. Perazzio, Nicolas de Albuquerque Weidebach and Anete S. Grumach
J. Fungi 2020, 6(4), 238; https://doi.org/10.3390/jof6040238 - 22 Oct 2020
Cited by 2 | Viewed by 2676
Abstract
Background: NADPH-oxidase and myeloperoxidase (MPO) play an important role on defense against pathogenic microorganisms. Defects on these mechanisms have been described in association with recurrent infections due to such as Staphylococcus aureus and Candida albicans. We describe a patient with partial disturbance [...] Read more.
Background: NADPH-oxidase and myeloperoxidase (MPO) play an important role on defense against pathogenic microorganisms. Defects on these mechanisms have been described in association with recurrent infections due to such as Staphylococcus aureus and Candida albicans. We describe a patient with partial disturbance of intracellular microorganism destruction clinically manifested by recurrent fungal infection. Case report and results: A 58-year-old male rural farmer has suffered with superficial mycosis affecting hands, nails and right ankle persisting for 20 years. He was treated with several antifungal drugs with no improvement. Mycological scraping isolated Trichophyton rubrum. Immunological evaluation showed impaired T cell proliferation to Candidin and impaired neutrophil burst oxidative after specific stimulation with Candida albicans. The patient’s DNA was extracted from peripheral blood leukocytes for whole exome sequencing (WES) analysis. Two heterozygous variants of undetermined significance were screened accordingly: (1) MPO A332V (c.995G>A; rs28730837); and (2) NCF1 G83R (c.247G>A; rs139225348). Conclusions: Functional leukocyte evaluation with heterozygous variants in MPO and NCF1 suggest that these defects were associated with the susceptibility to dermatophytosis in our patient. We have developed a fast, effective and safe trial for screening individuals with yeast infections. Full article
(This article belongs to the Special Issue Innate Immunity in Fungal Infections)
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