Surfactant protein D inhibits growth, alters cell surface polysaccharide exposure and immune activation potential of Aspergillus fumigatus

• Published in: Cell surface (Amsterdam) Vol. 8; p. 100072
• Main Authors: Wong, Sarah Sze Wah, Dellière, Sarah, Schiefermeier-Mach, Natalia, Lechner, Lukas, Perkhofer, Susanne, Bomme, Perrine, Fontaine, Thierry, Schlosser, Anders G., Sorensen, Grith L., Madan, Taruna, Kishore, Uday, Aimanianda, Vishukumar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2022; Elsevier
• Subjects: Aspergillus fumigatus; Cell wall; Innate immunity; Life Sciences; Microbiology and Parasitology; Mycology; Pattern-recognition receptor; Polysaccharides; Surfactant protein D; SP-D; Polysaccharides; IL; Surfactant protein D; GM; Innate immunity; GAG; Aspergillus fumigatus; PBMCs; Pattern-recognition receptor; Cell wall; GAG:, Galactosaminogalactan; GM:, Galactomannan; PBMCs:, Peripheral blood mononuclear cells; SP-D:, Surfactant protein-D; IL:, Interleukin
• ISSN: 2468-2330; 2468-2330
• DOI: 10.1016/j.tcsw.2022.100072

•Surfactant protein D (SP-D), a C-type lectin and a major humoral immune component in the human lung-alveoli, shows direct growth inhibitory effect on Aspergillus fumigatus, an airborne opportunistic fungal pathogen.•SP-D treatment modifies the surface architecture and cell wall polysaccharide exposure on the A. fumigatus hyphae.•A. fumigatus hyphae grown in presence of SP-D stimulate significantly lower secretions of pro-inflammatory cytokine, but higher anti-inflammatory cytokine and chemokine secretions upon interaction with immune cells, compared to hyphae grown without SP-D.•Increased permeability of A. fumigatus hyphae upon SP-D treatment leads to a better efficacy of voriconazole, an antifungal drug that has its target in the fungal cytosol. Humoral immunity plays a defensive role against invading microbes. However, it has been largely overlooked with respect to Aspergillus fumigatus, an airborne fungal pathogen. Previously, we have demonstrated that surfactant protein D (SP-D), a major humoral component in human lung-alveoli, recognizes A. fumigatus conidial surface exposed melanin pigment. Through binding to melanin, SP-D opsonizes conidia, facilitates conidial phagocytosis, and induces the expression of protective pro-inflammatory cytokines in the phagocytic cells. In addition to melanin, SP-D also interacts with galactomannan (GM) and galactosaminogalactan (GAG), the cell wall polysaccharides exposed on germinating conidial surfaces. Therefore, we aimed at unravelling the biological significance of SP-D during the germination process. Here, we demonstrate that SP-D exerts direct fungistatic activity by restricting A. fumigatus hyphal growth. Conidial germination in the presence of SP-D significantly increased the exposure of cell wall polysaccharides chitin, α-1,3-glucan and GAG, and decreased β-1,3-glucan exposure on hyphae, but that of GM was unaltered. Hyphae grown in presence of SP-D showed positive immunolabelling for SP-D. Additionally, SP-D treated hyphae induced lower levels of pro-inflammatory cytokine, but increased IL-10 (anti-inflammatory cytokine) and IL-8 (a chemokine) secretion by human peripheral blood mononuclear cells (PBMCs), compared to control hyphae. Moreover, germ tube surface modifications due to SP-D treatment resulted in an increased hyphal susceptibility to voriconazole, an antifungal drug. It appears that SP-D exerts its anti-A. fumigatus functions via a range of mechanisms including hyphal growth-restriction, hyphal surface modification, masking of hyphal surface polysaccharides and thus altering hyphal immunostimulatory properties.