The molecular immunology of human susceptibility to fungal diseases: lessons from single gene defects of immunity

Vinh, Donald C.

doi:10.1080/1744666x.2019.1584038

Cited by 7 publications

(8 citation statements)

References 243 publications

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“…Pheohyphomycetes (dematiaceous fungi) are environmentally distributed moulds that are darkly pigmented due to the presence of melanin in the fungal cell wall. The host–fungal interaction can result in three human syndromes: eumycotic mycetoma, chromoblastomycosis, and phaeohyphomycosis [ 443 ]. Eumycotic mycetoma is a chronic cutaneous/subcutaneous infection characterized by the triad of ‘tumefaction’ (i.e., the indolent appearance of inflammatory nodules/mass with fibrosis); the penetration of sinuses or fistulae into deep tissue; and presence of granules in tissue or discharge [ 444 ].…”

Section: Pheohyphomycosis (Dematiaceous Fungi)mentioning

confidence: 99%

Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases

Vinh

2023

Pathogens

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In medical mycology, the main context of disease is iatrogenic-based disease. However, historically, and occasionally, even today, fungal diseases affect humans with no obvious risk factors, sometimes in a spectacular fashion. The field of “inborn errors of immunity” (IEI) has deduced at least some of these previously enigmatic cases; accordingly, the discovery of single-gene disorders with penetrant clinical effects and their immunologic dissection have provided a framework with which to understand some of the key pathways mediating human susceptibility to mycoses. By extension, they have also enabled the identification of naturally occurring auto-antibodies to cytokines that phenocopy such susceptibility. This review provides a comprehensive update of IEI and autoantibodies that inherently predispose humans to various fungal diseases.

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Section: Pheohyphomycosis (Dematiaceous Fungi)mentioning

confidence: 99%

Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases

Vinh

2023

Pathogens

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“…We looked into variations introduced by SNPs that are present in the immune response genes ( Table 1 ) critical for fungal infections. The polymorphism in the immune genes ( PTX3, CX3CR1, CARD9 , STAT3 , and others, Figure 1 ) make the host susceptible ( Garlanda et al, 2002 ; Kumar et al, 2018 ; Vinh, 2019 ), and defect in interleukins (e.g., IL-4, IL-10) leads to genetic predisposition toward fungal infection ( Babula et al, 2005 ; Choi et al, 2005 ; Zaas, 2006 ; Table 1 ). The study of these genes helps us to understand the relationship between genetic polymorphism and the cellular phenotype of host, pathogen, and associated defense mechanisms ( Sardinha et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

“…CARD9 plays an important role in Th17 cell differentiation and helps in the release of cytokines ( Vautier et al, 2010 ; Speakman et al, 2020 ; Vornholz and Ruland, 2020 ). Recently, defects in CARD9 and STAT3 have been found to cause IFI with gastrointestinal manifestations ( Vinh, 2019 ) and mutation in STAT3 results in reduced Th17 cells causing candidiasis ( Engelhardt and Grimbacher, 2012 ). A heterozygous missense mutation in STAT1 is associated with coccidioidomycosis and histoplasmosis ( Sampaio et al, 2013 ).…”

Section: Genetic Polymorphism Of the Immune System Linked To Fungal Infectionsmentioning

confidence: 99%

Genetic Susceptibility to Fungal Infections and Links to Human Ancestry

et al. 2021

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Over the ages, fungi have associated with different parts of the human body and established symbiotic associations with their host. They are mostly commensal unless there are certain not so well-defined factors that trigger the conversion to a pathogenic state. Some of the factors that induce such transition can be dependent on the fungal species, environment, immunological status of the individual, and most importantly host genetics. In this review, we discuss the different aspects of how host genetics play a role in fungal infection since mutations in several genes make hosts susceptible to such infections. We evaluate how mutations modulate the key recognition between the pathogen associated molecular patterns (PAMP) and the host pattern recognition receptor (PRR) molecules. We discuss the polymorphisms in the genes of the immune system, the way it contributes toward some common fungal infections, and highlight how the immunological status of the host determines fungal recognition and cross-reactivity of some fungal antigens against human proteins that mimic them. We highlight the importance of single nucleotide polymorphisms (SNPs) that are associated with several of the receptor coding genes and discuss how it affects the signaling cascade post-infection, immune evasion, and autoimmune disorders. As part of personalized medicine, we need the application of next-generation techniques as a feasible option to incorporate an individual’s susceptibility toward invasive fungal infections based on predisposing factors. Finally, we discuss the importance of studying genomic ancestry and reveal how genetic differences between the human race are linked to variation in fungal disease susceptibility.

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“…The study of these rare diseases has provided us with a deeper understanding of the pathophysiologic mechanisms involved. Overall, alterations and imbalances of IL-17 and IL-22, and possibly IFN-γ, have been identified as important factors predisposing individuals to develop CMC [ 11 , 13 , 14 , 15 , 16 , 17 , 18 ] Figure 1 .…”

Section: Methodsmentioning

confidence: 99%

“…As stated above, patients with AR CARD9 deficiency are at risk for superficial and, more strikingly, invasive candidiasis (as well as other fungal infections). Importantly, these infections can manifest at any age [ 16 , 56 , 86 , 87 ]. The IC may affect various organs such as the bones, the gastrointestinal tract, and the eyes.…”

Section: Methodsmentioning

confidence: 99%

Inborn Errors of Immunity Causing Pediatric Susceptibility to Fungal Diseases

Olbrich

Vinh

2023

JoF

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Inborn errors of immunity are a heterogeneous group of genetically determined disorders that compromise the immune system, predisposing patients to infections, autoinflammatory/autoimmunity syndromes, atopy/allergies, lymphoproliferative disorders, and/or malignancies. An emerging manifestation is susceptibility to fungal disease, caused by yeasts or moulds, in a superficial or invasive fashion. In this review, we describe recent advances in the field of inborn errors of immunity associated with increased susceptibility to fungal disease.

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The molecular immunology of human susceptibility to fungal diseases: lessons from single gene defects of immunity

Cited by 7 publications

References 243 publications

Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases

Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases

Genetic Susceptibility to Fungal Infections and Links to Human Ancestry

Inborn Errors of Immunity Causing Pediatric Susceptibility to Fungal Diseases

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