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Title: | Fungal melanin stimulates surfactant protein D-mediated opsonization of and host immune response to Aspergillus fumigatus spores |
Authors: | Wah Wong, SS Rani, M Dodagatta-Marri, E Ibrahim-Granet, O Kishore, U Bayry, J Latgé, JP Sahu, A Madan, T Aimanianda, V |
Issue Date: | 5-Feb-2018 |
Citation: | Journal of Biological Chemistry, 2018, 293 (13), pp. 4901 - 4912 |
Abstract: | © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. 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. |
URI: | http://bura.brunel.ac.uk/handle/2438/17159 |
DOI: | http://dx.doi.org/10.1074/jbc.M117.815852 |
ISSN: | 0021-9258 http://dx.doi.org/10.1074/jbc.M117.815852 1083-351X |
Appears in Collections: | Dept of Life Sciences Embargoed Research Papers |
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