β-1,3-glucan-lacking Aspergillus fumigatus mediates an efficient antifungal immune response by activating complement and dendritic cells Article Swipe

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Marion Steger , Marta Bermejo‐Jambrina , Teodor E. Yordanov , Johannes Wagener , Axel A. Brakhage , Verena Pittl , Lukas A. Huber , Hubertus Haas , Cornelia Lass‐Flörl , Wilfried Posch , Doris Wilflingseder ·

YOU? · · 2018 · Open Access · · DOI: https://doi.org/10.6084/m9.figshare.7268435.v2

Complement system and dendritic cells (DCs) form – beside neutrophils and macrophages – the first line of defense to combat fungal infections. Therefore, we here studied interactions of these first immune elements with Aspergillus fumigatus lacking ß-1,3-glucans (fks1_tetOn^rep under repressed conditions) to mechanistically explain the mode of action of echinocandins in more detail. Echinocandins are cell wall active agents blocking β-glucan synthase, making the A. fumigatus fks1_tetOn mutant a good model to study immune-modulatory actions of these drugs. We now demonstrate herein, that complement was activated to significantly higher levels by the fks1-deficient strain compared to its respective wild type. This enhanced covalent linking of complement fragments to the A. fumigatus fks1_tetOn^rep mutant further resulted in enhanced DC binding and internalization of the fungus. Additionally, we found that fks1_tetOn^rep induced a Th1-/Th17-polarizing cytokine profile program in DCs. The effect was essentially dependent on massive galactomannan shedding, since blocking of DC-SIGN significantly reduced the fks1_tetOn^rep-mediated induction of an inflammatory cytokine profile. Our data demonstrate that lack of ß-1,3-glucan, also found under echinocandin therapy, results in improved recognition of Aspergillus fumigatus by complement and DCs and therefore not only directly affects the fungus by its fungistatic actions, but also is likely to exert indirect antifungal mechanisms by strengthening innate host immune mechanisms. Abbreviations: C: complement; CR:complement receptor; DC: dendritic cell; iDC: immature dendritic cell; DC-SIGN: Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; ERK: extracellular signal–regulated kinases; JNK : c-Jun N-terminal kinases; MAPK: mitogen-activated protein kinase; NHS: normal human serum; PRR: pattern recognition receptor; Th :T helper; TLR :Toll-like receptor; WT: wild type.

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Aspergillus Fumigatus

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Aspergillus fumigatus Antifungal Immune system Microbiology Complement (music) Glucan Biology Immunology Genetics Biochemistry Phenotype Complementation Gene

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Type: dataset
Language: en
Landing Page: https://doi.org/10.6084/m9.figshare.7268435.v2
OA Status: gold
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OpenAlex ID: https://openalex.org/W4394210310

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DOI: https://doi.org/10.6084/m9.figshare.7268435.v2

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Title: β-1,3-glucan-lacking Aspergillus fumigatus mediates an efficient antifungal immune response by activating complement and dendritic cells

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Language: en

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Publication year: 2018

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Publication date: 2018-01-01

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Authors: Marion Steger, Marta Bermejo‐Jambrina, Teodor E. Yordanov, Johannes Wagener, Axel A. Brakhage, Verena Pittl, Lukas A. Huber, Hubertus Haas, Cornelia Lass‐Flörl, Wilfried Posch, Doris Wilflingseder

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Landing page: https://doi.org/10.6084/m9.figshare.7268435.v2

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Concepts: Aspergillus fumigatus, Antifungal, Immune system, Microbiology, Complement (music), Glucan, Biology, Immunology, Genetics, Biochemistry, Phenotype, Complementation, Gene

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abstract_inverted_index.echinocandins	49
abstract_inverted_index.extracellular	230
abstract_inverted_index.fumigatus</i>	34, 178
abstract_inverted_index.galactomannan	144
abstract_inverted_index.significantly	87, 150
abstract_inverted_index.strengthening	205
abstract_inverted_index.<i>Aspergillus	33, 177
abstract_inverted_index.ß-1,3-glucan,	166
abstract_inverted_index.ß-1,3-glucans	36
abstract_inverted_index.internalization	120
abstract_inverted_index.mechanistically	42
abstract_inverted_index.immune-modulatory	73
abstract_inverted_index.mitogen-activated	239
abstract_inverted_index.signal–regulated	231
abstract_inverted_index.molecule-3-Grabbing	227
abstract_inverted_index.Th1-/Th17-polarizing	131
abstract_inverted_index.<b>Abbreviations</b>:	210
abstract_inverted_index.<i>fks1-</i>deficient	92
abstract_inverted_index.fks1<sub>tetOn</sub></i>	66
abstract_inverted_index.fks1<sub>tetOn</sub><sup>rep</sup></i>	111
abstract_inverted_index.<i>fks1<sub>tetOn</sub><sup>rep</sup></i>	128
abstract_inverted_index.(<i>fks1<sub>tetOn</sub><sup>rep</sup></i>	37
abstract_inverted_index.<i>fks1<sub>tetOn</sub><sup>rep</sup>-</i>mediated	153
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	11
citation_normalized_percentile