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

Sarah Sze Wah Wong; Sarah Dellière; Natalia Schiefermeier-Mach; Lukas Lechner; Susanne Perkhofer; Perrine Bomme; Thierry Fontaine; Anders G Schlosser; Grith L Sorensen; Taruna Madan; Uday Kishore; Vishukumar Aimanianda

doi:10.1016/j.tcsw.2022.100072

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

Cell Surf. 2022 Jan 10:8:100072. doi: 10.1016/j.tcsw.2022.100072. eCollection 2022 Dec.

Authors

Affiliations

¹ Institut Pasteur, Université de Paris, CNRS, Unité de Mycologie Moléculaire, UMR2000, F-75015 Paris, France.
² Department of Mycology & Parasitologie, Hôpital Saint-Louis, Paris, France.
³ Health University of Applied Sciences Tyrol/FH Gesundheit Tirol, Innrain 98, 6020 Innsbruck, Austria.
⁴ Ultrastructural Bio Imaging Unit, C2RT, Institut Pasteur, Paris, France.
⁵ Institut Pasteur, Université de Paris, INREA, USC2019, Unité Biologie et Pathogénicité Fongiques, F-75015 Paris, France.
⁶ Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
⁷ Department of Innate Immunity, ICMR-National Institute for Research in Reproductive and Child Health, Mumbai, India.
⁸ Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, United Kingdom.

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.

Keywords: Aspergillus fumigatus; Cell wall; GAG:, Galactosaminogalactan; GM:, Galactomannan; IL:, Interleukin; Innate immunity; PBMCs:, Peripheral blood mononuclear cells; Pattern-recognition receptor; Polysaccharides; SP-D:, Surfactant protein-D; Surfactant protein D.