Recognition of Fungal Components by the Host Immune System

2020 ◽  
Vol 21 (3) ◽  
pp. 245-264 ◽  
Author(s):  
Laura C. García-Carnero ◽  
José A. Martínez-Álvarez ◽  
Luis M. Salazar-García ◽  
Nancy E. Lozoya-Pérez ◽  
Sandra E. González-Hernández ◽  
...  

: By being the first point of contact of the fungus with the host, the cell wall plays an important role in the pathogenesis, having many molecules that participate as antigens that are recognized by immune cells, and also that help the fungus to establish infection. The main molecules reported to trigger an immune response are chitin, glucans, oligosaccharides, proteins, melanin, phospholipids, and others, being present in the principal pathogenic fungi with clinical importance worldwide, such as Histoplasma capsulatum, Paracoccidioides brasiliensis, Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, and Sporothrix schenckii. Knowledge and understanding of how the immune system recognizes and responds to fungal antigens are relevant for the future research and development of new diagnostic tools and treatments for the control of mycosis caused by these fungi.

1976 ◽  
Vol 3 (3) ◽  
pp. 272-276
Author(s):  
B J Phillips ◽  
W Kaplan

The effect of cetylpyridinium chloride (CPC) on pathogenic fungi and Nocardia asteroides was studied. Sputa seeded with each of 11 organisms (Aspergillus flavus; Aspergillus fumigatus, Blastomyces dermatitidis, Candida albicans, Coccidioides immitis, Cryptococcus neoformans, Geotrichum candidum, Histoplasma capsulatum; Nocardia asteroides, Paracoccidioides brasiliensis, and Sporothrix schenckii) were treated with CPC and kept for 2, 5 and 9 days. The CPC reagent used (0.5% CPC and 0.5% sodium chloride) is one the Mycobacteriolgoy Branch at the Center for Disease Control added to sputa before shipping them to laboratories for recovery of mycobacteria. None of the organisms tested survived this treatment, and none was recovered on mycological or mycobacteriological media. Seeded sputa containing these organisms were also tested with a second CPC reagent (0.02% CPC and 0.5% sodium chloride) and held for 2, 5 and 9 days. A few colonies of A. flavus, A. fumigatus, and N. asteroides were recovered from these samples. Neither the morphology of the fungi nor their stainability by the fluorescent antibody method was affected by treatment with the reagent containing 0.5% CPC. However, the background material in smears from the 0.5% CPC-treated samples retained the conjugate, and this made weakly fluorescing organisms more difficult to detect. The 0.5% CPC treatment did not alter the morphology of N. asteroides or its ability to be stained with Kinyoun acid-fast stain.


mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Mateus Silveira Freitas ◽  
Vânia Luiza Deperon Bonato ◽  
Andre Moreira Pessoni ◽  
Marcio L. Rodrigues ◽  
Arturo Casadevall ◽  
...  

ABSTRACT The release of extracellular vesicles (EVs) by fungi is a fundamental cellular process. EVs carry several biomolecules, including pigments, proteins, enzymes, lipids, nucleic acids, and carbohydrates, and are involved in physiological and pathological processes. EVs may play a pivotal role in the establishment of fungal infections, as they can interact with the host immune system to elicit multiple outcomes. It has been observed that, depending on the fungal pathogen, EVs can exacerbate or attenuate fungal infections. The study of the interaction between fungal EVs and the host immune system and understanding of the mechanisms that regulate those interactions might be useful for the development of new adjuvants as well as the improvement of protective immune responses against infectious or noninfectious diseases. In this review, we describe the immunomodulatory properties of EVs produced by pathogenic fungi and discuss their potential as adjuvants for prophylactic or therapeutic strategies.


2000 ◽  
Vol 38 (9) ◽  
pp. 3190-3193 ◽  
Author(s):  
Ralf Bialek ◽  
Aida Ibricevic ◽  
Annette Fothergill ◽  
Dominik Begerow

The similarities of paracoccidioidomycosis and blastomycosis are highly suggestive of a close relation of the two etiological agents. Whereas the agent of the first disease is exclusively endemic in Latin America, the agent of the latter one is endemic in North America and Africa. In symptomatic travelers visiting both areas of endemicity, differentiation of the diseases might be impossible, even though therapy and prognosis for these two diseases differ significantly. In order to identify differences in the 18S rRNA gene (rDNA) for use as molecular diagnostic tools, we sequenced this gene from five isolates of Paracoccidioides brasiliensis and compared them to known sequences of other fungi. Neighbor-joining, maximum parsimony, and maximum likelihood analyses and, finally, the Kishino-Hasegawa test revealed that P. brasiliensis, Blastomyces dermatitidis, and Emmonsia parva are more closely related than Histoplasma capsulatum and B. dermatitidis, whose teleomorphic forms belong to one genus,Ajellomyces. In accordance with the work of other investigators who have used internal transcribed spacer and large subunit rDNA sequences, our small subunit rDNA data show that the dimorphic fungus P. brasiliensis must be grouped within the order Onygenales and is closely related to members of the family Onygenaceae. There are hints in the molecular phylogenetic analysis that the family Onygenaceae might be further divided into two families. The subgroup that includes P. brasiliensis comprises all zoopathogenic species. The differences in the 18S rDNAs appear to be too small to allow species identification of the members of the family Onygenaceae pathogenic for humans by use of target sequences within this gene.


1998 ◽  
Vol 40 (3) ◽  
pp. 125-136 ◽  
Author(s):  
Cilmery Suemi KUROKAWA ◽  
Maria Fátima SUGIZAKI ◽  
Maria Terezinha Serrão PERAÇOLI

Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.


Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 667 ◽  
Author(s):  
Gaëlle Angrand ◽  
Alicia Quillévéré ◽  
Nadège Loaëc ◽  
Chrysoula Daskalogianni ◽  
Anton Granzhan ◽  
...  

Many pathogens (virus, bacteria, fungi, or parasites) have developed a wide variety of mechanisms to evade their host immune system. The budding yeast Saccharomyces cerevisiae has successfully been used to decipher some of these immune evasion strategies. This includes the cis-acting mechanism that limits the expression of the oncogenic Epstein–Barr virus (EBV)-encoded EBNA1 and thus of antigenic peptides derived from this essential but highly antigenic viral protein. Studies based on budding yeast have also revealed the molecular bases of epigenetic switching or recombination underlying the silencing of all except one members of extended families of genes that encode closely related and highly antigenic surface proteins. This mechanism is exploited by several parasites (that include pathogens such as Plasmodium, Trypanosoma, Candida, or Pneumocystis) to alternate their surface antigens, thereby evading the immune system. Yeast can itself be a pathogen, and pathogenic fungi such as Candida albicans, which is phylogenetically very close to S. cerevisiae, have developed stealthiness strategies that include changes in their cell wall composition, or epitope-masking, to control production or exposure of highly antigenic but essential polysaccharides in their cell wall. Finally, due to the high antigenicity of its cell wall, yeast has been opportunistically exploited to create adjuvants and vectors for vaccination.


Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2233-2240 ◽  
Author(s):  
Robert Zarnowski ◽  
Jon P. Woods

In this study, extracellular glutathione-dependent ferric reductase (GSH-FeR) activities in different dimorphic zoopathogenic fungal species were characterized. Supernatants from Blastomyces dermatitidis, Histoplasma capsulatum, Paracoccidioides brasiliensis and Sporothrix schenckii strains grown in their yeast form were able to reduce iron enzymically with glutathione as a cofactor. Some variations in the level of reduction were noted amongst the strains. This activity was stable in acidic, neutral and slightly alkaline environments and was inhibited when trivalent aluminium and gallium ions were present. Using zymography, single bands of GSH-FeRs with apparent molecular masses varying from 430 to 460 kDa were identified in all strains. The same molecular mass range was determined by size exclusion chromatography. These data demonstrate that dimorphic zoopathogenic fungi produce and secrete a family of similar GSH-FeRs that may be involved in the acquisition and utilization of iron. Siderophore production by these and other fungi has sometimes been considered to provide a full explanation of iron acquisition in these organisms. Our work reveals an additional common mechanism that may be biologically and pathogenically important. Furthermore, while some characteristics of these enzymes such as extracellular location, cofactor utilization and large size are not individually unique, when considered together and shared across a range of fungi, they represent an important novel physiological feature.


2021 ◽  
Author(s):  
Relber A Gonçales ◽  
Ayda LM Salamanca ◽  
Luiz RB Júnior ◽  
Kleber SF e Silva ◽  
Elton JR de Vasconcelos ◽  
...  

Aim: To predict glycosylphosphatidylinositol (GPI)-anchored proteins in the genome of Paracoccidioides brasiliensis and Paracoccidioides lutzii. Materials & methods: Five different bioinformatics tools were used for predicting GPI-anchored proteins; we considered as GPI-anchored proteins those detected by at least two in silico analysis methods. We also performed the proteomic analysis of P. brasiliensis cell wall by mass spectrometry. Results: Hundred GPI-anchored proteins were predicted in P. brasiliensis and P. lutzii genomes. A series of 57 proteins were classified in functional categories and 43 conserved proteins were reported with unknown functions. Four proteins identified by in silico analyses were also identified in the cell wall proteome. Conclusion: The data obtained in this study are important resources for future research of GPI-anchored proteins in Paracoccidioides spp. to identify targets for new diagnostic tools, drugs and immunological tests.


2004 ◽  
Vol 50 (6) ◽  
pp. 445-449 ◽  
Author(s):  
Renata Ferretti de Lima ◽  
Marcelly Maria dos Santos Brito ◽  
Guido Manoel Vidal Schäffer ◽  
Osana Cunha de Lima ◽  
Cintia de Moraes Borba

Morphological differentiation has commanded attention for its putative impact on the pathogenesis of invasive fungal infections. We evaluated in vitro and in vivo the dimorphism from mycelial to yeast-phase of Sporothrix schenckii, Blastomyces dermatitidis and Paracoccidioides brasiliensis isolates, two strains for each species, preserved in mineral oil. S. schenckii strains showed typical micromorphology at 25 °C but one strain was unable to complete the dimorphic process in vitro. After in vivo passage through mice the strains had the ability to turn into yeast-like cells and to form colonies on brain-heart infusion medium at 36 °C. B. dermatitidis strains grew as dirty white to brownish membranous colonies at 25 °C and their micromorphology showed thin filaments with single hyaline conidia. At 36 °C the colonies did not differ from those grown at 25 °C, but produced a transitional micromorphology. P. brasiliensis strains grew as cream-colored cerebriform colonies at 25 °C showing a transitional morphology. B. dermatitidis and P. brasiliensis strains did not turn into yeast-like cells in vivo. The present results demonstrate that B. dermatitidis and P. brasiliensis strains were unable to complete the dimorphic process even after in vivo passage, in contrast to the S. schenckii strain.Key words: pathogenic fungi, in vitro storage, in vivo passage, morphogenesis.


2007 ◽  
Vol 56 (6) ◽  
pp. 788-797 ◽  
Author(s):  
Robert Zarnowski ◽  
Makoto Miyazaki ◽  
Agnieszka Dobrzyn ◽  
James M. Ntambi ◽  
Jon P. Woods

The performance of fatty acid profiling for strain differentiation of Histoplasma capsulatum was assessed. Total fatty acids were isolated from the yeast-phase cells of seven stock and two previously unreported clinical strains of H. capsulatum var. capsulatum, as well as from one unreported clinical strain and one stock strain of H. capsulatum var. duboisii, and one strain of each of three other dimorphic zoopathogenic fungal species, Blastomyces dermatitidis, Paracoccidioides brasiliensis and Sporothrix schenckii. Different colony morphology and pigmentation types of the H. capsulatum strains were also included. The most frequently occurring fatty acids were oleic, palmitic, stearic and linoleic acids. There were variations in the relative percentage fatty acid contents of H. capsulatum strains that could be used for strain identification and discrimination. Differentiation between H. capsulatum strains was achieved by the comparison of detected fatty acids accompanied by principal component analysis using calculated Varimax-rotated principal component loadings. Statistical analysis yielded three major principal components that explained over 94 % of total variance in the data. All the strains of H. capsulatum var. capsulatum RFLP classes II and III were grouped into two distinct clusters: the heterogenic RFLP class I formed a large, but also well-defined group, whereas the outgroup strains of H. capsulatum var. duboisii, B. dermatitidis, P. brasiliensis and S. schenckii were shifted away. These data suggest that fatty acid profiling can be used in H. capsulatum strain classification and epidemiological studies that require strain differentiation at the intraspecies level.


Author(s):  
Diego de Souza Gonçalves ◽  
Claudia Rodriguez de La Noval ◽  
Marina da Silva Ferreira ◽  
Leandro Honorato ◽  
Glauber Ribeiro de Sousa Araújo ◽  
...  

The cell wall is a ubiquitous structure in the fungal kingdom, with some features varying depending on the species. Additional external structures can be present, such as the capsule of Cryptococcus neoformans (Cn), its major virulence factor, mainly composed of glucuronoxylomannan (GXM), with anti-phagocytic and anti-inflammatory properties. The literature shows that other cryptococcal species and even more evolutionarily distant species, such as the Trichosporon asahii, T. mucoides, and Paracoccidioides brasiliensis can produce GXM-like polysaccharides displaying serological reactivity to GXM-specific monoclonal antibodies (mAbs), and these complex polysaccharides have similar composition and anti-phagocytic properties to cryptococcal GXM. Previously, we demonstrated that the fungus Histoplasma capsulatum (Hc) incorporates, surface/secreted GXM of Cn and the surface accumulation of the polysaccharide enhances Hc virulence in vitro and in vivo. In this work, we characterized the ability of Hc to produce cellular-attached (C-gly-Hc) and secreted (E-gly) glycans with reactivity to GXM mAbs. These C-gly-Hc are readily incorporated on the surface of acapsular Cn cap59; however, in contrast to Cn GXM, C-gly-Hc had no xylose and glucuronic acid in its composition. Mapping of recognized Cn GXM synthesis/export proteins confirmed the presence of orthologs in the Hc database. Evaluation of C-gly and E-gly of Hc from strains of distinct monophyletic clades showed serological reactivity to GXM mAbs, despite slight differences in their molecular dimensions. These C-gly-Hc and E-gly-Hc also reacted with sera of cryptococcosis patients. In turn, sera from histoplasmosis patients recognized Cn glycans, suggesting immunogenicity and the presence of cross-reacting antibodies. Additionally, C-gly-Hc and E-gly-Hc coated Cn cap59 were more resistant to phagocytosis and macrophage killing. C-gly-Hc and E-gly-Hc coated Cn cap59 were also able to kill larvae of Galleria mellonella. These GXM-like Hc glycans, as well as those produced by other pathogenic fungi, may also be important during host-pathogen interactions, and factors associated with their regulation are potentially important targets for the management of histoplasmosis.


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