Indoleamine 2,3-dioxygenases (IDOs) degrade l-tryptophan to kynurenines and drive the de novo synthesis of nicotinamide adenine dinucleotide. Unsurprisingly, various invertebrates, vertebrates, and even fungi produce IDO. In mammals, IDO1 also serves as a homeostatic regulator, modulating immune response to infection via local tryptophan deprivation, active catabolite production, and non-enzymatic cell signaling. Whether fungal Idos have pleiotropic functions that impact on host-fungal physiology is unclear. Here, we show that Aspergillus fumigatus possesses three ido genes that are expressed under conditions of hypoxia or tryptophan abundance. Loss of these genes results in increased fungal pathogenicity and inflammation in a mouse model of aspergillosis, driven by an alternative tryptophan degradation pathway to indole derivatives and the host aryl hydrocarbon receptor. Fungal tryptophan metabolic pathways thus cooperate with the host xenobiotic response to shape host-microbe interactions in local tissue microenvironments.

• Klíčová slova
• AhR, Aspergillus fumigatus, IDO, IL-33, NAD, aspergillosis, indoles, inflammation, tryptophan,
• MeSH
• Aspergillus fumigatus patogenita   MeSH
• aspergilóza patofyziologie   MeSH
• lidé MeSH
• myši MeSH
• tryptofan metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• tryptofan MeSH

GOAL: Determination of basic epidemiological parameters of burn patients with micromycetes infection. Identification of the most important micromycetes in burn patients. MATERIAL AND METHODS: Monocentre retrospective study enrolling all adult burn patients who were hospitalized between 2007 and 2015 and in whom micromycetes were isolated during hospitalization. ABSI index (Abbreviated Burn Severity Index) was used to evaluate severity of thermal trauma. Results were statistically analysed. RESULTS: There were 61 patients with thermal trauma identified in total during the period of observation, and there were yeast or fibrous fungi isolated. There were 37 males and 24 females (M:F ratio - 1.5:1) in this group. The average age of patients was 57.3 years (29 patients were aged up to 60 years, 32 patients were over the age of 60 years, inclusive). 6 patients died (lethality was 9.8%). The average extent of the burn area was 21.6% TBSA (median 14.0%). There were 90 strains of micromycetes cultured in total in these patients (79 yeasts, 11 fibrous fungi). Micromycetes were isolated from burn area in 30 patients, from the lower airways in 19 patients, from the urogenital area in 15 patients and from blood culture in 7 patients. Non-albicans Candida species were predominant among yeasts (60 strains); Candida albicans was isolated 16 times in total. Aspergillus fumigatus (4 isolations) and Fusarium species (2 isolations) were predominant species among fibrous fungi. CONCLUSION: We successfully identified the basic epidemiological parameters in burn patients with micromycetes infection, similarly to the most important yeasts and fibrous fungi causing infection in these patients.

• Klíčová slova
• Burns, fibrous fungi infection., yeasts,
• MeSH
• Aspergillus fumigatus * izolace a purifikace   patogenita   MeSH
• Candida * izolace a purifikace   patogenita   MeSH
• dospělí MeSH
• hospitalizace MeSH
• lidé středního věku MeSH
• lidé MeSH
• popálení * mikrobiologie   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia.

• MeSH
• Aspergillus fumigatus imunologie   patogenita   MeSH
• dospělí MeSH
• fluorescenční protilátková technika MeSH
• fukosa metabolismus   MeSH
• fungální proteiny imunologie   metabolismus   MeSH
• lektiny imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• muciny imunologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• plicní aspergilóza imunologie   metabolismus   MeSH
• průtoková cytometrie MeSH
• slizniční imunita imunologie   MeSH
• spory hub imunologie   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• fucose-binding lectin MeSH Prohlížeč
• fukosa MeSH
• fungální proteiny MeSH
• lektiny MeSH
• muciny MeSH