Dexamethasone Promotes <i>Aspergillus fumigatus</i> Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2
Since long-term corticosteroid treatment is associated with emerging opportunistic fungal infections causing high morbidity and mortality in immune-suppressed individuals, here we characterized the impact of dexamethasone (Dex) treatment on <i>Aspergillus fumigatus</i>-related immune mod...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/7/2/70 |
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| author | Maureen K. Luvanda Wilfried Posch Jonathan Vosper Viktoria Zaderer Asma Noureen Cornelia Lass-Flörl Doris Wilflingseder |
| author_facet | Maureen K. Luvanda Wilfried Posch Jonathan Vosper Viktoria Zaderer Asma Noureen Cornelia Lass-Flörl Doris Wilflingseder |
| author_sort | Maureen K. Luvanda |
| collection | DOAJ |
| description | Since long-term corticosteroid treatment is associated with emerging opportunistic fungal infections causing high morbidity and mortality in immune-suppressed individuals, here we characterized the impact of dexamethasone (Dex) treatment on <i>Aspergillus fumigatus</i>-related immune modulation. We found by high content screening and flow cytometric analyses that during monocyte-to-macrophage differentiation, as little as 0.1 µg/mL Dex resulted in a shift in macrophage polarization from M1 to M2-like macrophages. This macrophage repolarization mediated via Dex was characterized by significant upregulation of the M2 marker CD163 and downmodulation of M1 markers CD40 and CD86 as well as changes in phenotypic properties and adherence. These Dex-mediated phenotypic alterations were furthermore associated with a metabolic switch in macrophages orchestrated via PKM2. Such treated macrophages lost their ability to prevent <i>Aspergillus fumigatus</i> germination, which was correlated with accelerated fungal growth, destruction of macrophages, and induction of an anti-inflammatory cytokine profile. Taken together, repolarization of macrophages following corticosteroid treatment and concomitant switch to an anti-inflammatory phenotype might play a prominent role in triggering invasive aspergillosis (IA) due to suppression of innate immunological responses necessary to combat extensive fungal outgrowth. |
| first_indexed | 2024-03-09T04:12:52Z |
| format | Article |
| id | doaj.art-71b62a0b80464e8aab8440d90558227c |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T04:12:52Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-71b62a0b80464e8aab8440d90558227c2023-12-03T13:57:47ZengMDPI AGJournal of Fungi2309-608X2021-01-01727010.3390/jof7020070Dexamethasone Promotes <i>Aspergillus fumigatus</i> Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2Maureen K. Luvanda0Wilfried Posch1Jonathan Vosper2Viktoria Zaderer3Asma Noureen4Cornelia Lass-Flörl5Doris Wilflingseder6Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaInstitute of Medical Biochemistry, Medical University of Innsbruck, 6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaSince long-term corticosteroid treatment is associated with emerging opportunistic fungal infections causing high morbidity and mortality in immune-suppressed individuals, here we characterized the impact of dexamethasone (Dex) treatment on <i>Aspergillus fumigatus</i>-related immune modulation. We found by high content screening and flow cytometric analyses that during monocyte-to-macrophage differentiation, as little as 0.1 µg/mL Dex resulted in a shift in macrophage polarization from M1 to M2-like macrophages. This macrophage repolarization mediated via Dex was characterized by significant upregulation of the M2 marker CD163 and downmodulation of M1 markers CD40 and CD86 as well as changes in phenotypic properties and adherence. These Dex-mediated phenotypic alterations were furthermore associated with a metabolic switch in macrophages orchestrated via PKM2. Such treated macrophages lost their ability to prevent <i>Aspergillus fumigatus</i> germination, which was correlated with accelerated fungal growth, destruction of macrophages, and induction of an anti-inflammatory cytokine profile. Taken together, repolarization of macrophages following corticosteroid treatment and concomitant switch to an anti-inflammatory phenotype might play a prominent role in triggering invasive aspergillosis (IA) due to suppression of innate immunological responses necessary to combat extensive fungal outgrowth.https://www.mdpi.com/2309-608X/7/2/70glucocorticoidsdexamethasonemacrophagesglycolytic pathwayPKM2<i>Aspergillus fumigatus</i> |
| spellingShingle | Maureen K. Luvanda Wilfried Posch Jonathan Vosper Viktoria Zaderer Asma Noureen Cornelia Lass-Flörl Doris Wilflingseder Dexamethasone Promotes <i>Aspergillus fumigatus</i> Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2 Journal of Fungi glucocorticoids dexamethasone macrophages glycolytic pathway PKM2 <i>Aspergillus fumigatus</i> |
| title | Dexamethasone Promotes <i>Aspergillus fumigatus</i> Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2 |
| title_full | Dexamethasone Promotes <i>Aspergillus fumigatus</i> Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2 |
| title_fullStr | Dexamethasone Promotes <i>Aspergillus fumigatus</i> Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2 |
| title_full_unstemmed | Dexamethasone Promotes <i>Aspergillus fumigatus</i> Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2 |
| title_short | Dexamethasone Promotes <i>Aspergillus fumigatus</i> Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2 |
| title_sort | dexamethasone promotes i aspergillus fumigatus i growth in macrophages by triggering m2 repolarization via targeting pkm2 |
| topic | glucocorticoids dexamethasone macrophages glycolytic pathway PKM2 <i>Aspergillus fumigatus</i> |
| url | https://www.mdpi.com/2309-608X/7/2/70 |
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