A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

Robinet, Pauline; Baychelier, Florence; Fontaine, Thierry; Pïcard, Capucine; Debré, Patrice; Vieillard, Vincent; Latgé, Jean‐Paul; Elbim, Carole

doi:10.4049/jimmunol.1303180

Cited by 67 publications

(58 citation statements)

References 65 publications

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“…For instance, Cryptococcus elaborates a dense polysaccharide capsule, which shields cell wall carbohydrates from detection by the immune system (15,16). As cell wall carbohydrates are the primary PAMPs in fungal pathogens, we focused our analysis on carbohydrates that are known or suspected to provoke an immune response in other fungal species, including mannan (17)(18)(19)(20), ␤-1,3-glucan (21-30), galactosaminogalactan (GAG) (31)(32)(33)(34)(35)(36), and chitin (37)(38)(39)(40)(41)(42)(43)(44)(45). Freshly harvested Exserohilum rostratum spores were grown in complete RPMI at 37°C with 5% CO 2 .…”

Section: Resultsmentioning

confidence: 99%

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

et al. 2017

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Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality. Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus on Exserohilum rostratum, a dematiaceous mold that caused 753 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosing Exserohilum. Despite a lack of phagocytosis, macrophage production of tumor necrosis factor alpha is triggered by hyphae but not spores and depends upon Dectin-1, a C-type lectin receptor. Dectin-1 is specifically recruited to the macrophage-hyphal interface but not the macrophage-spore interface due to differences in carbohydrate antigen expression between these two fungal forms. Corticosteroid and antifungal therapy perturb this response, resulting in decreased cytokine production. In vivo soft tissue infection in wild-type mice demonstrated that Exserohilum provokes robust neutrophilic and granulomatous inflammation capable of thwarting fungal growth. However, coadministration of methylprednisolone acetate results in robust hyphal tissue invasion and a significant reduction in immune cell recruitment. Our results suggest that Dectin-1 is crucial for macrophage recognition and the macrophage response to Exserohilum and that corticosteroids potently attenuate the immune response to this pathogen.

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Section: Resultsmentioning

confidence: 99%

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

et al. 2017

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“…Second, GAG appeared to reduce neutrophil infiltrates in the lung during infection. GAG induced neutrophil apoptosis [17]. It was shown that polymorphonuclear leukocyte (PMN) apoptosis occur via a NK cell-dependent mechanism.…”

Section: Gag Is a Virulence Factor In A Fumigatusmentioning

confidence: 99%

Aspergillus Cell Wall and Biofilm

et al. 2014

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The fungal cell is surrounded by a cell wall that acts as a sieve and a reservoir for effector molecules that play an active role during infection. This cell wall is essential for fungal growth as well as for resisting host defense mechanisms. The Aspergillus fumigatus cell wall is almost exclusively composed of polysaccharides. The fibrillar core is composed of a branched β-(1,3)-glucan to which chitin, β-(1,3)-/β-(1,4)-glucan, and galactomannan are covalently bound. The alkali-soluble amorphous fraction is mainly composed of α-(1,3)-glucan that has adhesive property and stabilizes the cell wall. Although the same polysaccharides are found in the cell wall of different A. fumigatus morphotypes (conidia and hyphae), their concentration and localization are different. Conidial (the morphotype that mainly enters host respiratory system) cell wall is covered by an outer layer of rodlets and melanin, which confers hydrophobic properties and imparts immunological inertness. In contrast, outer layer of the hypha contains galactosaminogalactan, recently identified as an A. fumigatus virulence factor. The hypha grows either as a network of agglutinated and hydrophobic mass (called mycelium) embedded in an extracellular matrix (ECM) rich in polysaccharides, hydrophobin, and melanin or segregated without ECM.

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“…Remarkably, this mutant has been described as hyperadhesive to epithelial cells [18], and this hyperadhesive phenotype was further shown to be related to GAG. In addition, due to its immunomodulatory properties, GAG has also been described as an important virulence factor [20,21,22].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Modifications to the composition of the hyphal outer layer of Aspergillus fumigatus modulates HUVEC proteins related to inflammatory and stress responses

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Curty

Kubitschek-Barreira

et al. 2017

Journal of Proteomics

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A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

Cited by 67 publications

References 65 publications

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

Aspergillus Cell Wall and Biofilm

Modifications to the composition of the hyphal outer layer of Aspergillus fumigatus modulates HUVEC proteins related to inflammatory and stress responses

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