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The glycobiology of fungal cell wall polysaccharides and its relation in host immune response

Abstract : Objective: Aspergillus fumigatus is a ubiquitous fungal pathogen that can cause a wide range of infections, for example, invasive pulmonary aspergillosis (IPA) and allergic bronchopulmonary aspergillosis (ABPA). IPA was previously observed to mainly occur among immunocompromised populations, however, in recent years, more cases have been observed in otherwise immunocompetent patients. Therefore, it is important to elucidate the relationship between the fungal pathogen and the host immune system. In addition, in ABPA patients, other underlying pulmonary conditions are usually concurrently present, which challenge the normal clearance mechanism of conidia by phagocytes. As a result, the conidia are allowed to swell and germinate. Dormant conidia possess a layer of rodlet and melanin that masks the underneath polysaccharides in the cell wall. As the conidia swell, this outer layer disappears and the cell wall polysaccharides are exposed and are free to interact with the host immune system. Polysaccharides have been considered immunogenic. But the relationship between the glycobiology and host immune response is not well studied. In this study, the aim is to examine the effect of the length, linkage and solubility of galactomannan and alpha-1,3-glucan with the host immune response. Methods: Galactomannan oligosaccharides of different length and linkage and alpha-1,3-glucan oligosaacharides were synthesized. Native polysaccharides of galactomannan and alpha-1,3-glucan are also extracted from the A. fumigatus mycelia. All the oligosaccharides and native polysaccharides were immobilized or directly inoculated to microtite plates with PBMCs isolated from healthy donors. The stimulation was performed in the presence or absence of normal human serum, to investigate the significance of soluble mediators. The supernatant was collected after 24-h incubation and stored at -20C for further analysis of the cytokine induction. Results: The degree of cytokine induction is directly proportional to the length of both galactomannan and alpha-1,3-glucan. The short oligosaccharides and the native polysaccharides display several differences. The short oligosaccharides have to be immobilized (that is, insoluble, since free short oligosaccharides are soluble) and provided with serum for stimulation of cytokine production, while the native polysaccharides do not have to be immobilized and serum is not required. Conclusion: The length and solubility of cell wall polysaccharides are important factors in modulation the cytokine induction. Humoral immune factors, such as soluble mediators, may play a significant role in the recognition of short oligosaccharides, but not for the longer counterpart. Taken together, there exists a link between the glycobiology of A. fumigatus cell wall polysaccharides and the host immune response.
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Contributor : Anne Lassailly-Bondaz <>
Submitted on : Tuesday, April 7, 2020 - 11:44:06 AM
Last modification on : Tuesday, April 7, 2020 - 11:46:52 AM

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  • HAL Id : pasteur-02534824, version 1

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Sarah S. W. Wong, Vishukumar Aimanianda, Jean-Paul Latgé. The glycobiology of fungal cell wall polysaccharides and its relation in host immune response. 20th Congress of the International Society for Human and Animal Mycology, Jun 2018, Amsterdam, Netherlands. pp.416. ⟨pasteur-02534824⟩

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