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

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

doi:10.1016/j.tcsw.2022.100072

Cited by 8 publications

(7 citation statements)

References 69 publications

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“…suggesting their importance in host–pathogen interaction by being either consumed, degraded by the fungus or initially deficient and a potential risk factor. These findings confirmed and deepened previous knowledge on certain humoral components and identified promising leads that resulted in major findings, especially on SP-D [ 49 ]. Metabolomics.…”

Section: Introductionsupporting

confidence: 86%

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Humoral Immunity Against Aspergillus fumigatus

Dellière

Aimanianda

2023

Mycopathologia

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Aspergillus fumigatus is one the most ubiquitous airborne opportunistic human fungal pathogens. Understanding its interaction with host immune system, composed of cellular and humoral arm, is essential to explain the pathobiology of aspergillosis disease spectrum. While cellular immunity has been well studied, humoral immunity has been poorly acknowledge, although it plays a crucial role in bridging the fungus and immune cells. In this review, we have summarized available data on major players of humoral immunity against A. fumigatus and discussed how they may help to identify at-risk individuals, be used as diagnostic tools or promote alternative therapeutic strategies. Remaining challenges are highlighted and leads are given to guide future research to better grasp the complexity of humoral immune interaction with A. fumigatus.

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Section: Introductionsupporting

confidence: 86%

“…SP-D opsonized conidia are phagocytosed more efficiently and stimulated the secretion of pro-inflammatory cytokines by hMDMs [ 48 ]. Furthermore, SP-D exerts direct fungistatic activity by restricting hyphal growth and induces hyphal surface modifications associated to increased susceptibility of the fungus to voriconazole [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

Humoral Immunity Against Aspergillus fumigatus

Dellière

Aimanianda

2023

Mycopathologia

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“…Likewise, mouse models and case series showed potential for granulocyte-macrophage colony-stimulating factor (GM-CSF) in IA, but a randomized phase IV clinical trial could not show benefit for GM-CSF with or without granulocyte colony-stimulating factor (G-CSF) as prophylaxis for IA after allogeneic stem cell transplantation [109,[120][121][122][123]. Administration of other humoral innate immune agents such as pentraxin-3 (PTX3) or surfactant-protein D (SP-D) are protective in vitro and/or in mice, but their potential for treatment of IA has not been investigated yet in a clinical setting [124][125][126][127].…”

Section: Immunotherapymentioning

confidence: 99%

Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading

et al. 2023

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Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients and hence vulnerable hosts increases, which is paralleled by the emergence of a rise in IA cases. Increased frequencies of azole-resistant strains are reported from six continents, presenting a new challenge for the therapeutic management. Treatment options for IA currently consist of three classes of antifungals (azoles, polyenes, echinocandins) with distinctive advantages and shortcomings. Especially in settings of difficult to treat IA, comprising drug tolerance/resistance, limiting drug–drug interactions, and/or severe underlying organ dysfunction, novel approaches are urgently needed. Promising new drugs for the treatment of IA are in late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix (a Gwt1 enzyme inhibitor), ibrexafungerp (a triterpenoid), opelconazole (an azole optimized for inhalation) and rezafungin (an echinocandin with long half-life time). Further, new insights in the pathophysiology of IA yielding immunotherapy as a potential add-on therapy. Current investigations show encouraging results, so far mostly in preclinical settings. In this review we discuss current treatment strategies, give an outlook on possible new pharmaceutical therapeutic options, and, lastly, provide an overview of the ongoing research in immunotherapy for IA.

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“…Swollen conidia and culture filtrates were prepared as described before [42,47]. In short, to obtain swollen conidia, 10 8 freshly isolated conidia/mL were incubated in RPMI plus 3.45% MOPS (Fisher Scientific, Vienna, Austria) plus 2% glucose (Merck KGaA, Darmstadt, Germany) on an environmental shaker-incubator ES-20/60 (BioSan, Riga, Latvia) at 37 • C and maintained at 160 rpm for 2 h. Swollen conidia were further diluted for experiments to the desired concentration, as stated below.…”

Section: Cell Treatmentsmentioning

confidence: 99%

“…In addition, the binding of the hydrophilic SP led to agglutination of A. fumigatus conidia, preventing the dissemination of conidia, thus enhancing phagocytosis by macrophages and neutrophils [8,40]. It was observed that SP-D could directly bind both A. fumigatus conidia and hyphae, further inhibiting fungal growth [42].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Surfactant Protein Gene Expression by Aspergillus fumigatus in NCl-H441 Cells

et al. 2023

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Aspergillus fumigatus is an opportunistic fungal pathogen that causes serious lung diseases in immunocompromised patients. The lung surfactant produced by alveolar type II and Clara cells in the lungs is an important line of defense against A. fumigatus. The surfactant consists of phospholipids and surfactant proteins (SP-A, SP-B, SP-C and SP-D). The binding to SP-A and SP-D proteins leads to the agglutination and neutralization of lung pathogens as well as the modulation of immune responses. SP-B and SP-C proteins are essential for surfactant metabolism and can modulate the local immune response; however, the molecular mechanisms remain unclear. We investigated changes in the SP gene expression in human lung NCI-H441 cells infected with conidia or treated with culture filtrates obtained from A. fumigatus. To further identify fungal cell wall components that may affect the expression of SP genes, we examined the effect of different A. fumigatus mutant strains, including dihydroxynaphthalene (DHN)-melanin-deficient ΔpksP, galactomannan (GM)-deficient Δugm1 and galactosaminogalactan (GAG)-deficient Δgt4bc strains. Our results show that the tested strains alter the mRNA expression of SP, with the most prominent and consistent downregulation of the lung-specific SP-C. Our findings also suggest that secondary metabolites rather than the membrane composition of conidia/hyphae inhibit SP-C mRNA expression in NCI-H441 cells.

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

Cited by 8 publications

References 69 publications

Humoral Immunity Against Aspergillus fumigatus

Humoral Immunity Against Aspergillus fumigatus

Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading

Regulation of Surfactant Protein Gene Expression by Aspergillus fumigatus in NCl-H441 Cells

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