Search Results (12)

Allergic conditions have surged to unprecedented levels globally, affecting approximately 30% of the population. Fungi are among the major sources of allergens, accounting for about 6% of respiratory issues. Identifying the causes of respiratory allergies is not always possible. Our study assessed the capacity of two plant parasites, Podosphaera fusca and Peronospora ficariae, which infect Cucurbita pepo and Ficaria verna, to provoke inflammatory and asthmatic reactions in mouse models of acute and chronic asthma. We performed experiments by sensitizing mice through intranasal challenges with extracts from P. fusca and P. ficariae. Subsequently, we used ELISA tests to measure pro-inflammatory cytokines, including IL-4, IL-5, IL-13, TNF-α, and TGF-β. We evaluated specific IgE production through ELISA and examined histological changes in mouse lungs using hematoxylin-eosin staining. Our research revealed that P. fusca and P. ficariae induced significant production of all tested cytokines, increased specific IgE levels, and caused histological changes characteristic of acute and chronic asthma progression. Although weaker than the reference allergen ovalbumin, P. fusca and P. ficariae possess proinflammatory and asthma-inducing capabilities, indicating the potential to expand the current list of fungal allergens. Full article

Background and Clinical Significance: Since the prevalence of fungal lung infections is increasing, certain agents, such as Cladosporium spp., have emerged as unexpected causes. Cladosporium spp. fungi are ubiquitous in environments such as soil, fruits, and wine corks; they are a part of the normal human skin flora; and they are known respiratory allergens. Case Presentation: A patient with a history of post-COVID-19 syndrome and AIDS presented with lung pathology indicative of an invasive fungal infection. The initial histopathological examination revealed numerous yeast-like cells with narrow-based budding, which led to a mistaken diagnosis of cryptococcosis. However, further detailed examination revealed sparse hyphae in the lung tissue, suggesting a more complex fungal infection. Molecular analyses and sequence BLAST alignment were performed, ultimately identifying the infectious agent as “Cladosporium species novum”, a rare cause of invasive pulmonary cladosporiasis. Conclusions: Invasive pulmonary cladosporiasis is a rare condition, and the morphological features of the fungus alone were insufficient to establish a correct diagnosis. A comprehensive pathohistological and molecular approach with bioinformatics tools is essential for the correct identification of rare and potentially life-threatening fungal pathogens in immunocompromised patients. Full article

L-asparaginase is an essential drug used to treat acute lymphoid leukemia (ALL), a cancer of high prevalence in children. Several adverse reactions associated with L-asparaginase have been observed, mainly caused by immunogenicity and allergenicity. Some strategies have been adopted, such as searching for new microorganisms that produce the enzyme and applying protein engineering. Therefore, this work aimed to elucidate the molecular structure and predict the immunogenic profile of L-asparaginase from Penicillium cerradense, recently revealed as a new fungus of the genus Penicillium and producer of the enzyme, as a motivation to search for alternatives to bacterial L-asparaginase. In the evolutionary relationship, L-asparaginase from P. cerradense closely matches Aspergillus species. Using in silico tools, we characterized the enzyme as a protein fragment of 378 amino acids (39 kDa), including a signal peptide containing 17 amino acids, and the isoelectric point at 5.13. The oligomeric state was predicted to be a homotetramer. Also, this L-asparaginase presented a similar immunogenicity response (T- and B-cell epitopes) compared to Escherichia coli and Dickeya chrysanthemi enzymes. These results suggest a potentially useful L-asparaginase, with insights that can drive strategies to improve enzyme production. Full article

Atopic dermatitis, or eczema, is the most common chronic skin disorder, characterized by red and pruritic lesions. Its etiology is multifaceted, involving an interplay of factors, such as the allergic immune response, skin barrier dysfunction, and dysbiosis of the skin microbiota. Recent studies have explored the role of extracellular vesicles (EVs), which are lipid bilayer-delimitated particles released by all cells, in atopic dermatitis. Examination of the available literature identified that most studies investigated EVs released by Staphylococcus aureus, which were found to impact the skin barrier and promote the release of cytokines that contribute to atopic dermatitis development. In addition, EVs released by the skin fungus, Malassezia sympodialis, were found to contain allergens, suggesting a potential contribution to allergic sensitization via the skin. The final major finding was the role of EVs released by mast cells, which were capable of activating various immune cells and attenuating the allergic response. While research in this area is still in its infancy, the studies examined in this review provide encouraging insights into how EVs released from a variety of cells play a role in both contributing to and protecting against atopic dermatitis. Full article

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron–quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo– or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated K_d values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo– and holo–Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation. Full article

Aspergillus is a genus of saprophytic fungus widely distributed in the environment and associated with soil, decaying vegetation, or seeds. However, some species, such as A. fumigatus, are considered opportunistic pathogens in humans. Their conidia (asexual spores) and mycelia are associated with clinical diseases known as invasive aspergillosis (IA), mainly related to the respiratory tract, such as allergic asthma, allergic bronchopulmonary aspergillosis (ABPA), or hypersensitivity. However, they can also disseminate to other organs, particularly the central nervous system. Due to the dispersal mechanism of the conidia through the air, airborne fungal particle measurement should be used to prevent and control this mold. This study aims to measure the outdoor airborne concentration of Aspergillus conidia and the Asp f 1 allergen concentration in Bellaterra (Barcelona, Spain) during 2021 and 2022, and to compare their dynamics to improve the understanding of the biology of this genus and contribute to a better diagnosis, prevention, and therapeutic measures in the face of possible health problems. The results show that both particles were airborne nearly all year round, but their concentrations showed no correlation. Due to Asp f 1 not being present in the conidia itself but being detectable during their germination and in hyphal fragments, we report the relevance of the aero-immunological analysis as a methodology to detect the potential pathogenic hazard of this fungus. Full article

Fungal allergy is the third most frequent cause of respiratory pathologies and the most related to a poor prognosis of asthma. The genera Alternaria and Cladosporium are the most frequently associated with allergic respiratory diseases, with Alternaria being the one with the highest prevalence of sensitization. Alternaria alternata is an outdoor fungus whose spores disseminate in warm and dry air, reaching peak levels in temperate summers. Alternaria can also be found in damp and insufficiently ventilated houses, causing what is known as sick building syndrome. Thus, exposure to fungal allergens can occur outdoors and indoors. However, not only spores but also fungal fragments contain detectable amounts of allergens and may function as aeroallergenic sources. Allergenic extracts of Alternaria hyphae and spores are still in use for the diagnosis and treatment of allergic diseases but are variable and insufficiently standardised, as they are often a random mixture of allergenic ingredients and casual impurities. Thus, diagnosis of fungal allergy has been difficult, and knowledge about new fungal allergens is stuck. The number of allergens described in Fungi remains almost constant while new allergens are being found in the Plantae and Animalia kingdoms. Given Alt a 1 is not the unique Alternaria allergen eliciting allergy symptoms, component-resolved diagnosis strategies should be applied to diagnose fungal allergy. To date, twelve A. alternata allergens are accepted in the WHO/IUIS Allergen Nomenclature Subcommittee, many of them are enzymes: Alt a 4 (disulfide isomerase), Alt a 6 (enolase), Alt a 8 (mannitol de-hydrogenase), Alt a 10 (aldehyde dehydrogenase), Alt a 13 (glutathione-S-transferase) and Alt a MnSOD (Mn superoxide dismutase), and others have structural and regulatory functions such as Alt a 5 and Alt a 12, Alt a 3, Alt a 7. The function of Alt a 1 and Alt a 9 remains unknown. Other four allergens are included in other medical databases (e.g., Allergome): Alt a NTF2, Alt a TCTP, and Alt a 70 kDa. Despite Alt a 1 being the A. alternata major allergen, other allergens, such as enolase, Alt a 6 or MnSOD, Alt a 14 have been suggested to be included in the diagnosis panel of fungal allergy. Full article

Objective. We hypothesized that, in our REPRO_PL cohort, exposure to indoor allergens and lifestyle factors in early life are associated with risk of asthma, atopic dermatitis, and allergic rhinitis at ten years of age. Methods. We only examined children who had lived in the same house from birth. Children’s exposure to tobacco smoke was assessed based on cotinine levels in urine. House dust samples were collected. Results. Higher Fel d1 concentration in house dust was associated with significantly higher risk of developing asthma at age 10 years (95% CI,10.87 to 20.93; p < 0.001). Frequent house cleaning was associated with development of atopic dermatitis (odds ratio 0.61; 95% CI 0.37 to 0.99; p = 0.045). Clustering of exposure to HDM revealed two types of environment. Cluster 1, defined as lower HDM (dust), in contrast to Cluster 2, defined as higher HDM, was characterized by old-type windows, lower fungus and dampness levels, as well as more frequent house cleaning. Conclusion. Exposure to cat allergens and new-type buildings that limit air flow while increasing the condensation of steam on the windows and thereby stimulating the growth of fungi are risk factors for the development of asthma. Full article

In nature, there are many species of fungi known to produce various mycotoxins, allergens and volatile organic compounds (VOCs), as well as the commonly known etiological agents of various types of mycoses. So far, none of them have provoked so much emotion among homeowners, builders, conservators, mycologists and clinicians as Stachybotrys chartarum. This species compared to fungi of the genera Fusarium and Aspergillus is not as frequently described to be a micromycete that is toxigenic and hazardous to human and animal health, but interest in it has been growing consistently for three decades. Depending on the authors of any given review article, attention is focused either on the clinical aspects alongside the role of this fungus in deterioration of biomaterials, or aspects related to its biology, ecology and taxonomic position. On the one hand, it is well established that inhalation of conidia, containing the highest concentrations of toxic metabolites, may cause serious damage to the mammalian lung, particularly with repeated exposure. On the other hand, we can find articles in which authors demonstrate that S. chartarum conidia can germinate and form hyphae in lungs but are not able to establish an effective infection. Finally, we can find case reports that suggest that S. chartarum infection is linked with acute pulmonary hemorrhage, based on fungal structures recovered from patient lung tissue. New scientific reports have verified the current state of knowledge and note that clinical significance of this fungus is exceedingly controversial. For these reasons, understanding S. chartarum requires reviewing the well-known toxigenic features and harmful factors associated with this fungus, by gathering the newest ones into a coherent whole. The research problem related to this fungus seems to be not overly publicized, and there is still a demand to truthfully define the real threats of S. chartarum and phylogenetically related species. The most important problem, which should be fully elucidated as soon as possible, remains the clarification of the pathogenicity of S. chartarum and related species. Maybe it is urgent time to ask a critical question, namely what exactly do we know 28 years after the outbreak of pulmonary hemorrhage in infants in Cleveland, Ohio, USA most likely caused by S. chartarum? Full article

Alternaria alternata is the most important allergenic fungus, with up to 20% of allergic patients affected. The sensitization profile of patients sensitized to A. alternata and how it changes when treated with immunotherapy is not known. Our objective is to determine the allergen recognition pattern of allergic patients to A. alternata and to study its association to the parameters studied in a clinical trial recently published. Sera of 64 patients from the clinical trial of immunotherapy with native major allergen Alt a 1 were analyzed by immunoblotting; 98. 4% of the patients recognized Alt a 1. The percentage of recognition for Alt a 3, Alt a 4, and/or Alt a 6, Alt a 7, Alt a 8, Alt a 10 and/or Alt a 15 was 1.6%, 21.9%, 12.5%, 12.5%, and 12.5% respectively. Of the 64 patients, 45 (70.3%) only recognized Alt a 1 among the allergens present in the A. alternata extract. Immunotherapy with Alt a 1 desensitizes treated patients, reducing their symptoms and medication consumption through the elimination of Alt a 1 sensitization, which is no longer present in the immunoblotting of some patients. There may be gender differences in the pattern of sensitization to A. alternata allergens, among others. Full article

Sparassis crispa is a kind of edible fungus widely grows in the north temperate zone, which shows various medicinal properties. Due to the complexity of chemical constitutes of this species, few investigations have acquired a comprehensive configuration for the chemical profile of it. In this study, a strategy based on ultra-high performance liquid chromatography (UPLC) combined with Orbitrap mass spectrometer (MS) was established for rapidly characterizing various chemical components in S. crispa. Through the summarized MS/MS fragmentation patterns of reference compounds and systematic identification strategy, a total of 110 components attributed to six categories were identified for the first time. Moreover, allergic rhinitis (AR) is a worldwide inflammatory disease seriously affecting human health, and the development of drugs to treat AR has been a topic of interest. It has been reported that the extracts of S. crispa showed obvious inhibitory effects on degranulation of mast cell- and allergen-induced IgE and proinflammatory mediators, but the active components and specific mechanism were still not clear. Src family kinases (SFKs) participate in the initial stage of allergy occurrence, which are considered the targets of AR treatment. Herein, on the basis of that self-built chemical database, virtual screening was applied to predict the potential SFKs inhibitors in S. crispa, using known crystal structures of Hck, Lyn, Fyn, and Syk as receptors, followed by the anti-inflammatory activity evaluation for screened hits by intracellular calcium mobilization assay. As results, sparoside A was directly confirmed to have strong anti-inflammatory activity with an IC₅₀ value of 5.06 ± 0.60 μM. This study provides a useful elucidation for the chemical composition of S. crispa, and demonstrated its potential inhibitory effects on AR, which could promote the research and development of effective agents from natural resources. Full article

One of the most commonly encountered species in the small basidiomycetous sub-phylum Wallemiomycotina is Wallemia mellicola, a xerotolerant fungus with a widespread distribution. To investigate the population characteristics of the species, whole genomes of twenty-five strains were sequenced. Apart from identification of four strains of clonal origin, the distances between the genomes failed to reflect either the isolation habitat of the strains or their geographical origin. Strains from different parts of the world appeared to represent a relatively homogenous and widespread population. The lack of concordance between individual gene phylogenies and the decay of linkage disequilibrium indicated that W. mellicola is at least occasionally recombining. Two versions of a putative mating-type locus have been found in all sequenced genomes, each present in approximately half of the strains. W. mellicola thus appears to be capable of (sexual) recombination and shows no signs of allopatric speciation or specialization to specific habitats. Full article