Elsevier

The Cell Surface

Volume 8, December 2022, 100072
The Cell Surface

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

https://doi.org/10.1016/j.tcsw.2022.100072Get rights and content
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open access

Highlights

  • 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.

Abstract

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.

Abbreviations

SP-D:
Surfactant protein-D
GM:
Galactomannan
GAG:
Galactosaminogalactan
IL:
Interleukin
PBMCs:
Peripheral blood mononuclear cells

Keywords

Aspergillus fumigatus
Innate immunity
Pattern-recognition receptor
Surfactant protein D
Cell wall
Polysaccharides

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