Regulation of Surfactant Protein Gene Expression by <i>Aspergillus fumigatus</i> in NCl-H441 Cells
<i>Aspergillus fumigatus</i> 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 <i>A. fumigatus</i>. The sur...
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MDPI AG
2023-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/4/1011 |
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| author | Natalia Schiefermeier-Mach Lea Heinrich Lukas Lechner Susanne Perkhofer |
| author_facet | Natalia Schiefermeier-Mach Lea Heinrich Lukas Lechner Susanne Perkhofer |
| author_sort | Natalia Schiefermeier-Mach |
| collection | DOAJ |
| description | <i>Aspergillus fumigatus</i> 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 <i>A. fumigatus</i>. 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 <i>A. fumigatus</i>. To further identify fungal cell wall components that may affect the expression of SP genes, we examined the effect of different <i>A. fumigatus</i> mutant strains, including dihydroxynaphthalene (DHN)-melanin-deficient <i>ΔpksP</i>, galactomannan (GM)-deficient <i>Δugm1</i> and galactosaminogalactan (GAG)-deficient <i>Δgt4bc</i> 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. |
| first_indexed | 2024-03-11T04:43:10Z |
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| last_indexed | 2024-03-11T04:43:10Z |
| publishDate | 2023-04-01 |
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| spelling | doaj.art-02a867aecd334a53b74ef9fe0171b53d2023-11-17T20:33:42ZengMDPI AGMicroorganisms2076-26072023-04-01114101110.3390/microorganisms11041011Regulation of Surfactant Protein Gene Expression by <i>Aspergillus fumigatus</i> in NCl-H441 CellsNatalia Schiefermeier-Mach0Lea Heinrich1Lukas Lechner2Susanne Perkhofer3Research and Innovation Unit, Health University of Applied Sciences Tyrol/FH Gesundheit Tirol, 6020 Innsbruck, AustriaResearch and Innovation Unit, Health University of Applied Sciences Tyrol/FH Gesundheit Tirol, 6020 Innsbruck, AustriaResearch and Innovation Unit, Health University of Applied Sciences Tyrol/FH Gesundheit Tirol, 6020 Innsbruck, AustriaResearch and Innovation Unit, Health University of Applied Sciences Tyrol/FH Gesundheit Tirol, 6020 Innsbruck, Austria<i>Aspergillus fumigatus</i> 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 <i>A. fumigatus</i>. 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 <i>A. fumigatus</i>. To further identify fungal cell wall components that may affect the expression of SP genes, we examined the effect of different <i>A. fumigatus</i> mutant strains, including dihydroxynaphthalene (DHN)-melanin-deficient <i>ΔpksP</i>, galactomannan (GM)-deficient <i>Δugm1</i> and galactosaminogalactan (GAG)-deficient <i>Δgt4bc</i> 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.https://www.mdpi.com/2076-2607/11/4/1011<i>Aspergillus fumigatus</i>lung surfactant proteinNCI-H441 cells |
| spellingShingle | Natalia Schiefermeier-Mach Lea Heinrich Lukas Lechner Susanne Perkhofer Regulation of Surfactant Protein Gene Expression by <i>Aspergillus fumigatus</i> in NCl-H441 Cells Microorganisms <i>Aspergillus fumigatus</i> lung surfactant protein NCI-H441 cells |
| title | Regulation of Surfactant Protein Gene Expression by <i>Aspergillus fumigatus</i> in NCl-H441 Cells |
| title_full | Regulation of Surfactant Protein Gene Expression by <i>Aspergillus fumigatus</i> in NCl-H441 Cells |
| title_fullStr | Regulation of Surfactant Protein Gene Expression by <i>Aspergillus fumigatus</i> in NCl-H441 Cells |
| title_full_unstemmed | Regulation of Surfactant Protein Gene Expression by <i>Aspergillus fumigatus</i> in NCl-H441 Cells |
| title_short | Regulation of Surfactant Protein Gene Expression by <i>Aspergillus fumigatus</i> in NCl-H441 Cells |
| title_sort | regulation of surfactant protein gene expression by i aspergillus fumigatus i in ncl h441 cells |
| topic | <i>Aspergillus fumigatus</i> lung surfactant protein NCI-H441 cells |
| url | https://www.mdpi.com/2076-2607/11/4/1011 |
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