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Immunity to Human Fungal Pathogens
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Immunity to Human Fungal Pathogens

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 25635

Special Issue Editors

Dr. Amariliz Rivera

E-Mail Website
Guest Editor
Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, USA
Interests: innate antifungal immune; pulmonary fungal disease
Dr. Karen Wozniak

E-Mail Website
Guest Editor
Department of Microbiology and Molecular Genetics, Oklahoma State University, 307 Life Science East, Stillwater, OK 74078, USA
Interests: fungal infections; Cryptococcus neoformans; fungal immunology
Dr. Michal A. Olszewski

E-Mail Website
Guest Editor
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, and VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA
Interests: antifungal immunity; immunopathology; host-pathogen interactions; pathogenesis; virulence mechanisms; adaptive and innate immunity

Special Issue Information

Dear Colleagues,

Opportunistic fungal infections in immunocompromised individuals either resulting from natural causes or immunosuppressive therapies are a growing health concern, and outbreaks of infections caused by endemic fungi are not uncommon and can be equally as devastating as in the immunocompromised. In either case, properly directed immune responses are needed to protect the host by eradicating the fungus and limiting collateral damage and immunopathology. Despite significant advances in understanding how immune cell subsets interact with and eliminate fungi or permit their growth, a greater understanding is required, the areas of intense research including the interactions of specific virulence-associated fungal genes with the immune system, diversities of the local responses in various tissues,  immune dysregulation, immunomodulation in response to immunotherapies and the use of biomarkers to stratify the patients into the appropriate treatment groups. Host immune system interactions by fungal products dissect new pathogenicity drivers and uncover novel aspects of host–pathogen mechanism interactions. The aim of this Special Issue is to focus on the mechanistic and clinically relevant aspects of host interactions with fungal pathogens, including cellular and molecular responses of antifungal immunity, leading to host protection or immunopathology, topics including, but not limited to, fungus–immune cell interactions, host and pathogen factors contributing to fungal diseases, antifungal immunity, altered susceptibility to fungal pathogens resulting from immunotherapies and pathogenicity drivers of disease caused by these fungi.

Dr. Amariliz Rivera
Dr. Karen Wozniak
Dr. Michal A. Olszewski
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

  • fungal infections
  • immune dysregulation
  • host–pathogen interaction
  • antifungal immunity
  • fungal diseases

Published Papers (6 papers)

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Research

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11 pages, 1394 KiB  
Article
Effect of Flagellin Pre-Exposure on the Inflammatory and Antifungal Response of Bronchial Epithelial Cells to Fungal Pathogens
by Jeanne Bigot, Manon Ruffin, Juliette Guitard, Sandra Vellaissamy, Sophie Thorez, Harriet Corvol, Loïc Guillot, Viviane Balloy and Christophe Hennequin
J. Fungi 2022, 8(12), 1268; https://doi.org/10.3390/jof8121268 - 30 Nov 2022
Viewed by 1412
Abstract
Bronchial epithelial cells (BEC) play a crucial role in innate immunity against inhaled fungi. Indeed, in response to microorganisms, BEC synthesize proinflammatory cytokines involved in the recruitment of neutrophils. We have recently shown that BEC exert antifungal activity against Aspergillus fumigatus by inhibiting [...] Read more.
Bronchial epithelial cells (BEC) play a crucial role in innate immunity against inhaled fungi. Indeed, in response to microorganisms, BEC synthesize proinflammatory cytokines involved in the recruitment of neutrophils. We have recently shown that BEC exert antifungal activity against Aspergillus fumigatus by inhibiting filament growth. In the present study, we first analyzed the inflammatory and antifungal responses of BEC infected by several fungal species such as Aspergillus spp., Scedosporium apiospermum and Candida albicans, which are frequently isolated from the sputum of people with chronic pulmonary diseases. The airways of these patients, such as people with cystic fibrosis (pwCF), are mainly colonized by P. aeruginosa and secondary by fungal pathogens. We have previously demonstrated that BEC are capable of innate immune memory, allowing them to increase their inflammatory response against A. fumigatus following a previous contact with Pseudomonas aeruginosa flagellin. To identify the impact of bacteria exposure on BEC responses to other fungal infections, we extended the analysis of BEC innate immune memory to Aspergillus spp., Scedosporium apiospermum and Candida albicans infection. Our results show that BEC are able to recognize and respond to Aspergillus spp., S. apiospermum and C. albicans infection and that the modulation of BEC responses by pre-exposure to flagellin varies according to the fungal species encountered. Deepening our knowledge of the innate immune memory of BEC should open new therapeutic avenues to modulate the inflammatory response against polymicrobial infections observed in chronic pulmonary diseases such as CF. Full article
(This article belongs to the Special Issue Immunity to Human Fungal Pathogens)
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Review

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16 pages, 2484 KiB  
Review
Dendritic Cells: Multifunctional Roles in Host Defenses to Cryptococcus Infections
by Kristie D. Goughenour, Ayesha S. Nair, Jintao Xu, Michal A. Olszewski and Karen L. Wozniak
J. Fungi 2023, 9(11), 1050; https://doi.org/10.3390/jof9111050 - 26 Oct 2023
Cited by 1 | Viewed by 1268
Abstract
Fungal infections are an increasingly growing public health concern, and Cryptococcus is one of the most problematic fungal organisms causing substantial mortality and morbidity worldwide. Clinically, this high incidence of cryptococcosis is most commonly seen in immunocompromised patients, especially those who lack an [...] Read more.
Fungal infections are an increasingly growing public health concern, and Cryptococcus is one of the most problematic fungal organisms causing substantial mortality and morbidity worldwide. Clinically, this high incidence of cryptococcosis is most commonly seen in immunocompromised patients, especially those who lack an adaptive T cell response, such as HIV/AIDS patients. However, patients with other underlying immunodeficiencies are also at an increased risk for cryptococcosis. The adaptive immune response, in particular the Th1/Th17 T-cell-mediated responses, to pulmonary Cryptococcus infections are required for host protection. Dendritic cells (DCs), encompassing multiple subsets identified to date, are recognized as the major professional antigen-presenting cell (APC) subset essential for the initiation and execution of T-cell immunity. Apart from their prominent role in orchestration of the adaptive arm of the immune defenses, DCs are fully armed cells from the innate immune system capable of the recognition, uptake, and killing of the fungal cells. Thus, DCs serve as a critical point for the endpoint outcomes of either fungal control or unrestrained fungal infection. Multiple studies have shown that DCs are required for anti-cryptococcal defense in the lungs. In addition, the role of DCs in Cryptococcus gattii infections is just starting to be elucidated. C. gattii has recently risen to prominence with multiple outbreaks in the US and Canada, demonstrating increased virulence in non-immunocompromised individuals. C. gattii infection fails to generate an inflammatory immune response or a protective Th1/Th17 T cell response, at least in part, through a lack of proper DC function. Here we summarize the multiple roles of DCs, including subsets of DCs in both mouse and human models, the roles of DCs during cryptococcal infection, and mechanisms by cryptococcal cells to attempt to undermine these host defenses. Full article
(This article belongs to the Special Issue Immunity to Human Fungal Pathogens)
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20 pages, 816 KiB  
Review
Human Airway Epithelium Responses to Invasive Fungal Infections: A Critical Partner in Innate Immunity
by Arianne J. Crossen, Rebecca A. Ward, Jennifer L. Reedy, Manalee V. Surve, Bruce S. Klein, Jayaraj Rajagopal and Jatin M. Vyas
J. Fungi 2023, 9(1), 40; https://doi.org/10.3390/jof9010040 - 27 Dec 2022
Cited by 5 | Viewed by 2965
Abstract
The lung epithelial lining serves as the primary barrier to inhaled environmental toxins, allergens, and invading pathogens. Pulmonary fungal infections are devastating and carry high mortality rates, particularly in those with compromised immune systems. While opportunistic fungi infect primarily immunocompromised individuals, endemic fungi [...] Read more.
The lung epithelial lining serves as the primary barrier to inhaled environmental toxins, allergens, and invading pathogens. Pulmonary fungal infections are devastating and carry high mortality rates, particularly in those with compromised immune systems. While opportunistic fungi infect primarily immunocompromised individuals, endemic fungi cause disease in immune competent and compromised individuals. Unfortunately, in the case of inhaled fungal pathogens, the airway epithelial host response is vastly understudied. Furthering our lack of understanding, very few studies utilize primary human models displaying pseudostratified layers of various epithelial cell types at air-liquid interface. In this review, we focus on the diversity of the human airway epithelium and discuss the advantages and disadvantages of oncological cell lines, immortalized epithelial cells, and primary epithelial cell models. Additionally, the responses by human respiratory epithelial cells to invading fungal pathogens will be explored. Future investigations leveraging current human in vitro model systems will enable identification of the critical pathways that will inform the development of novel vaccines and therapeutics for pulmonary fungal infections. Full article
(This article belongs to the Special Issue Immunity to Human Fungal Pathogens)
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21 pages, 1582 KiB  
Review
Cryptococcus neoformans Infection in the Central Nervous System: The Battle between Host and Pathogen
by Yanli Chen, Zoe W. Shi, Ashley B. Strickland and Meiqing Shi
J. Fungi 2022, 8(10), 1069; https://doi.org/10.3390/jof8101069 - 12 Oct 2022
Cited by 21 | Viewed by 9061
Abstract
Cryptococcus neoformans (C. neoformans) is a pathogenic fungus with a global distribution. Humans become infected by inhaling the fungus from the environment, and the fungus initially colonizes the lungs. If the immune system fails to contain C. neoformans in the lungs, [...] Read more.
Cryptococcus neoformans (C. neoformans) is a pathogenic fungus with a global distribution. Humans become infected by inhaling the fungus from the environment, and the fungus initially colonizes the lungs. If the immune system fails to contain C. neoformans in the lungs, the fungus can disseminate to the blood and invade the central nervous system, resulting in fatal meningoencephalitis particularly in immunocompromised individuals including HIV/AIDS patients. Following brain invasion, C. neoformans will encounter host defenses involving resident as well as recruited immune cells in the brain. To overcome host defenses, C. neoformans possesses multiple virulence factors capable of modulating immune responses. The outcome of the interactions between the host and C. neoformans will determine the disease progression. In this review, we describe the current understanding of how C. neoformans migrates to the brain across the blood–brain barrier, and how the host immune system responds to the invading organism in the brain. We will also discuss the virulence factors that C. neoformans uses to modulate host immune responses. Full article
(This article belongs to the Special Issue Immunity to Human Fungal Pathogens)
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20 pages, 1142 KiB  
Review
A Fun-Guide to Innate Immune Responses to Fungal Infections
by Thomas B. Burgess, Alison M. Condliffe and Philip M. Elks
J. Fungi 2022, 8(8), 805; https://doi.org/10.3390/jof8080805 - 29 Jul 2022
Cited by 9 | Viewed by 8289
Abstract
Immunocompromised individuals are at high risk of developing severe fungal infections with high mortality rates, while fungal pathogens pose little risk to most healthy people. Poor therapeutic outcomes and growing antifungal resistance pose further challenges for treatments. Identifying specific immunomodulatory mechanisms exploited by [...] Read more.
Immunocompromised individuals are at high risk of developing severe fungal infections with high mortality rates, while fungal pathogens pose little risk to most healthy people. Poor therapeutic outcomes and growing antifungal resistance pose further challenges for treatments. Identifying specific immunomodulatory mechanisms exploited by fungal pathogens is critical for our understanding of fungal diseases and development of new therapies. A gap currently exists between the large body of literature concerning the innate immune response to fungal infections and the potential manipulation of host immune responses to aid clearance of infection. This review considers the innate immune mechanisms the host deploys to prevent fungal infection and how these mechanisms fail in immunocompromised hosts. Three clinically relevant fungal pathogens (Candida albicans, Cryptococcus spp. and Aspergillus spp.) will be explored. This review will also examine potential mechanisms of targeting the host therapeutically to improve outcomes of fungal infection. Full article
(This article belongs to the Special Issue Immunity to Human Fungal Pathogens)
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Other

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12 pages, 2494 KiB  
Brief Report
Differential Transcriptional Responses of Human Granulocytes to Fungal Infection with Candida albicans and Aspergillus fumigatus
by Tilman E. Klassert, Martin Hölzer, Cristina Zubiria-Barrera, Julia Bethge, Esther Klaile, Mario M. Müller, Manja Marz and Hortense Slevogt
J. Fungi 2023, 9(10), 1014; https://doi.org/10.3390/jof9101014 - 14 Oct 2023
Viewed by 1579
Abstract
Neutrophils are critical phagocytic cells in innate immunity, playing a significant role in defending against invasive fungal pathogens. This study aimed to explore the transcriptional activation of human neutrophils in response to different fungal pathogens, including Candida albicans and Aspergillus fumigatus, compared [...] Read more.
Neutrophils are critical phagocytic cells in innate immunity, playing a significant role in defending against invasive fungal pathogens. This study aimed to explore the transcriptional activation of human neutrophils in response to different fungal pathogens, including Candida albicans and Aspergillus fumigatus, compared to the bacterial pathogen Escherichia coli. We identified distinct transcriptional profiles and stress-related pathways in neutrophils during fungal infections, highlighting their functional diversity and adaptability. The transcriptional response was largely redundant across all pathogens in immune-relevant categories and cytokine pathway activation. However, differences in the magnitude of differentially expressed genes (DEGs) were observed, with A. fumigatus inducing a lower transcriptional effect compared to C. albicans and E. coli. Notably, specific gene signatures associated with cell death were differentially regulated by fungal pathogens, potentially increasing neutrophil susceptibility to autophagy, pyroptosis, and neutrophil extracellular trap (NET) formation. These findings provide valuable insights into the complex immunological responses of neutrophils during fungal infections, offering new avenues for diagnostic and therapeutic strategies, particularly in the management of invasive fungal diseases. Full article
(This article belongs to the Special Issue Immunity to Human Fungal Pathogens)
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