Mannan detecting C-type lectin receptor probes recognise immune epitopes with diverse chemical, spatial and phylogenetic heterogeneity in fungal cell walls
| Autor: | Maria Spyrou, Angelina S. Palma, Wengang Chai, Janet A. Willment, Neil A. R. Gow, Yan Liu, Gordon D. Brown, Mark H. T. Stappers, Ingrida Vendele, Ten Feizi, Lisete M. Silva |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Fungal Structure
Yeast and Fungal Models Immune receptor Pathology and Laboratory Medicine Immune Receptors Biochemistry CYSTEINE-RICH DOMAIN Epitope Mannans C-type lectin Cell Wall 1108 Medical Microbiology Medicine and Health Sciences Biology (General) Receptor Phylogeny Candida Fungal Pathogens 0303 health sciences Immune System Proteins Chemistry Pattern recognition receptor Eukaryota Cell biology Experimental Organism Systems Medical Microbiology INFECTIONS 1107 Immunology Saccharomyces Cerevisiae PATHOGENIC FUNGUS Pathogens Cellular Structures and Organelles BETA-GLUCAN Life Sciences & Biomedicine N-GLYCANS Mannose receptor Research Article Signal Transduction 0605 Microbiology Cell Binding Cell Physiology QH301-705.5 Immunology MANNOSE RECEPTOR Receptors Cell Surface chemical and pharmacologic phenomena Mycology Research and Analysis Methods Microbiology DC-SIGN 03 medical and health sciences Saccharomyces Immune system Cell Walls Model Organisms HOST-DEFENSE Virology Genetics Candida Albicans Humans Lectins C-Type Molecular Biology Microbial Pathogens 030304 developmental biology CANDIDA-ALBICANS DECTIN-1 Innate immune system Science & Technology 030306 microbiology Organisms Fungi Biology and Life Sciences Proteins Cell Biology RC581-607 Yeast Mycoses Animal Studies Parasitology Immunologic diseases. Allergy Pattern Recognition Receptors Cell Adhesion Molecules |
| Zdroj: | Vendele, I, Willment, J A, Silva, L M, Palma, A S, Chai, W, Liu, Y, Feizi, T, Spyrou, M, Stappers, M H T, Brown, G D & Gow, N A R 2020, ' Mannan detecting C-type lectin receptor probes recognise immune epitopes with diverse chemical, spatial and phylogenetic heterogeneity in fungal cell walls ', PLoS Pathogens, vol. 16, no. 1, pp. e1007927 . https://doi.org/10.1371/journal.ppat.1007927 PLoS Pathogens PLoS Pathogens, Vol 16, Iss 1, p e1007927 (2020) |
| DOI: | 10.1371/journal.ppat.1007927 |
| Popis: | During the course of fungal infection, pathogen recognition by the innate immune system is critical to initiate efficient protective immune responses. The primary event that triggers immune responses is the binding of Pattern Recognition Receptors (PRRs), which are expressed at the surface of host immune cells, to Pathogen-Associated Molecular Patterns (PAMPs) located predominantly in the fungal cell wall. Most fungi have mannosylated PAMPs in their cell walls and these are recognized by a range of C-type lectin receptors (CTLs). However, the precise spatial distribution of the ligands that induce immune responses within the cell walls of fungi are not well defined. We used recombinant IgG Fc-CTLs fusions of three murine mannan detecting CTLs, including dectin-2, the mannose receptor (MR) carbohydrate recognition domains (CRDs) 4–7 (CRD4-7), and human DC-SIGN (hDC-SIGN) and of the β-1,3 glucan-binding lectin dectin-1 to map PRR ligands in the fungal cell wall of fungi grown in vitro in rich and minimal media. We show that epitopes of mannan-specific CTL receptors can be clustered or diffuse, superficial or buried in the inner cell wall. We demonstrate that PRR ligands do not correlate well with phylogenetic relationships between fungi, and that Fc-lectin binding discriminated between mannosides expressed on different cell morphologies of the same fungus. We also demonstrate CTL epitope differentiation during different phases of the growth cycle of Candida albicans and that MR and DC-SIGN labelled outer chain N-mannans whilst dectin-2 labelled core N-mannans displayed deeper in the cell wall. These immune receptor maps of fungal walls of in vitro grown cells therefore reveal remarkable spatial, temporal and chemical diversity, indicating that the triggering of immune recognition events originates from multiple physical origins at the fungal cell surface. Author summary Invasive fungal infections remain an important health problem in immunocompromised patients. Immune recognition of fungal pathogens involves binding of specific cell wall components by pathogen recognition receptors (PRRs) and subsequent activation of immune defences. Some cell wall components are conserved among fungal species while other components are species-specific and phenotypically diverse. The fungal cell wall is dynamic and capable of changing its composition and organization when adapting to different growth niches and environmental stresses. Differences in the composition of the cell wall lead to differential immune recognition by the host. Understanding how changes in the cell wall composition affect recognition by PRRs is likely to be of major diagnostic and clinical relevance. Here we address this fundamental question using four soluble immune receptor-probes which recognize mannans and β-glucan in the cell wall. We use this novel methodology to demonstrate that mannan epitopes are differentially distributed in the inner and outer layers of fungal cell wall in a clustered or diffuse manner. Immune reactivity of fungal cell surfaces was not correlated with relatedness of different fungal species, and mannan-detecting receptor-probes discriminated between cell surface mannans generated by the same fungus growing under different conditions. These studies demonstrate that mannan-epitopes on fungal cell surfaces are differentially distributed within and between the cell walls of fungal pathogens. |
| Databáze: | OpenAIRE |
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