Fungal melanin stimulates surfactant protein D–mediated opsonization of and host immune response to Aspergillus fumigatus spores - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2018

Fungal melanin stimulates surfactant protein D–mediated opsonization of and host immune response to Aspergillus fumigatus spores

Résumé

Surfactant protein D (SP-D), a C-type lectin and pattern-recognition soluble factor, plays an important role in immune surveillance to detect and eliminate human pulmonary pathogens. SP-D has been shown to protect against infections with the most ubiquitous airborne fungal pathogen, Aspergillus fumigatus, but the fungal surface component(s) interacting with SP-D is unknown. Here, we show that SP-D binds to melanin pigment on the surface of A. fumigatus dormant spores (conidia). SP-D also exhibited an affinity to two cell-wall polysaccharides of A. fumigatus, galactomannan (GM) and galactosaminogalactan (GAG). The immunolabeling pattern of SP-D was punctate on the conidial surface and was uniform on germinating conidia, in accordance with the localization of melanin, GM, and GAG. We also found that the collagen-like domain of SP-D is involved in its interaction with melanin, whereas its carbohydrate-recognition domain recognized GM and GAG. Unlike un-opsonized conidia, SP-D-opsonized conidia were phagocytosed more efficiently and stimulated the secretion of proinflammatory cytokines by human monocyte-derived macrophages. Furthermore, SP-D-/- mice challenged intranasally with wildtype conidia or melanin ghosts (i.e. hollow melanin spheres) displayed significantly reduced proinflammatory cytokines in the lung compared with wildtype mice. In summary, SP-D binds to melanin present on the dormant A. fumigatus conidial surface, facilitates conidial phagocytosis, and stimulates the host immune response.

Dates et versions

inserm-02455446 , version 1 (26-01-2020)

Identifiants

Citer

Sarah Sze Wah Wong, Manjusha Rani, Eswari Dodagatta-Marri, Oumaïma Ibrahim-Granet, Uday Kishore, et al.. Fungal melanin stimulates surfactant protein D–mediated opsonization of and host immune response to Aspergillus fumigatus spores. Journal of Biological Chemistry, 2018, 293 (13), pp.4901-4912. ⟨10.1074/jbc.M117.815852⟩. ⟨inserm-02455446⟩
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