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

Abstract : 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.
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https://www.hal.inserm.fr/inserm-02455446
Contributor : Jagadeesh Bayry <>
Submitted on : Sunday, January 26, 2020 - 11:02:37 AM
Last modification on : Thursday, April 9, 2020 - 11:56:37 AM

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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, American Society for Biochemistry and Molecular Biology, 2018, 293 (13), pp.4901-4912. ⟨10.1074/jbc.M117.815852⟩. ⟨inserm-02455446⟩

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