Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure
Abstract Soil-transmitted helminths (STH) are widespread, with Ascaris lumbricoides infecting millions globally. Malaria and STH co-infections are common in co-endemic regions. Artemisinin derivatives (ARTs)—artesunate, artemether, and dihydroartemisinin—are standard malaria treatments and are also...
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2025-01-01
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| author | Zaneta D. Musimbi Arkadi Kundik Jürgen Krücken Anja E. Hauser Sebastian Rausch Peter H. Seeberger Raluca Niesner Ruth Leben Susanne Hartmann |
| author_facet | Zaneta D. Musimbi Arkadi Kundik Jürgen Krücken Anja E. Hauser Sebastian Rausch Peter H. Seeberger Raluca Niesner Ruth Leben Susanne Hartmann |
| author_sort | Zaneta D. Musimbi |
| collection | DOAJ |
| description | Abstract Soil-transmitted helminths (STH) are widespread, with Ascaris lumbricoides infecting millions globally. Malaria and STH co-infections are common in co-endemic regions. Artemisinin derivatives (ARTs)—artesunate, artemether, and dihydroartemisinin—are standard malaria treatments and are also known to influence the energy metabolism of parasites, tumors, and immune cells. Herein, we explore the potential of ARTs to influence ascariasis either by directly targeting larvae or indirectly by modifying macrophage responses. Ascaris suum third-stage larvae and porcine IL-4 polarized (M2-like) macrophages were exposed to ARTs in vitro, and their metabolism was evaluated using two-photon NAD(P)H-FLIM. Both larvae and M2-like macrophages exhibited a steady-state bioenergetic profile of high oxidative phosphorylation and low anaerobic glycolysis. In A. suum larvae, two metabolically distinct regions were identified, with particularly high DUOX activity in the pharynx compared to the midgut; however, ARTs did not alter these profiles. In contrast, exposure of M2-like macrophages to ARTs induced a metabolic shift towards high anaerobic glycolysis and reduced metabolic activity, suggesting a possible indirect effect of ARTs on the helminth infection. Overall, two-photon NAD(P)H-FLIM proved to be a powerful tool for studying specific metabolic pathways in Ascaris larvae and host macrophages, offering valuable insights into the metabolic mechanisms of drug action on both parasite and host. |
| format | Article |
| id | doaj-art-ca068cf8b65640818c9505a70289e934 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-ca068cf8b65640818c9505a70289e9342025-01-19T12:23:02ZengNature PortfolioScientific Reports2045-23222025-01-0115111610.1038/s41598-025-85780-yTwo-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposureZaneta D. Musimbi0Arkadi Kundik1Jürgen Krücken2Anja E. Hauser3Sebastian Rausch4Peter H. Seeberger5Raluca Niesner6Ruth Leben7Susanne Hartmann8Institute of Immunology, Centre of Infection Medicine, Freie Universität BerlinInstitute of Immunology, Centre of Infection Medicine, Freie Universität BerlinInstitute for Parasitology and Tropical Veterinary Medicine, Freie Universität BerlinDepartment of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinInstitute of Immunology, Centre of Infection Medicine, Freie Universität BerlinMax Planck Institute of Colloids and InterfacesBiophysical Analytics, Deutsches Rheuma-Forschungszentrum (DRFZ)Institute of Immunology, Centre of Infection Medicine, Freie Universität BerlinInstitute of Immunology, Centre of Infection Medicine, Freie Universität BerlinAbstract Soil-transmitted helminths (STH) are widespread, with Ascaris lumbricoides infecting millions globally. Malaria and STH co-infections are common in co-endemic regions. Artemisinin derivatives (ARTs)—artesunate, artemether, and dihydroartemisinin—are standard malaria treatments and are also known to influence the energy metabolism of parasites, tumors, and immune cells. Herein, we explore the potential of ARTs to influence ascariasis either by directly targeting larvae or indirectly by modifying macrophage responses. Ascaris suum third-stage larvae and porcine IL-4 polarized (M2-like) macrophages were exposed to ARTs in vitro, and their metabolism was evaluated using two-photon NAD(P)H-FLIM. Both larvae and M2-like macrophages exhibited a steady-state bioenergetic profile of high oxidative phosphorylation and low anaerobic glycolysis. In A. suum larvae, two metabolically distinct regions were identified, with particularly high DUOX activity in the pharynx compared to the midgut; however, ARTs did not alter these profiles. In contrast, exposure of M2-like macrophages to ARTs induced a metabolic shift towards high anaerobic glycolysis and reduced metabolic activity, suggesting a possible indirect effect of ARTs on the helminth infection. Overall, two-photon NAD(P)H-FLIM proved to be a powerful tool for studying specific metabolic pathways in Ascaris larvae and host macrophages, offering valuable insights into the metabolic mechanisms of drug action on both parasite and host.https://doi.org/10.1038/s41598-025-85780-y |
| spellingShingle | Zaneta D. Musimbi Arkadi Kundik Jürgen Krücken Anja E. Hauser Sebastian Rausch Peter H. Seeberger Raluca Niesner Ruth Leben Susanne Hartmann Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure Scientific Reports |
| title | Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure |
| title_full | Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure |
| title_fullStr | Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure |
| title_full_unstemmed | Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure |
| title_short | Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure |
| title_sort | two photon nad p h flim reveals unperturbed energy metabolism of ascaris suum larvae in contrast to host macrophages upon artemisinin derivatives exposure |
| url | https://doi.org/10.1038/s41598-025-85780-y |
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