Prof. Dr. Raluca Niesner, Institute of Veterinary Physiology, Freie Universität Berlin

Ascarids are known to change their metabolism during their life cycle (1,2). During infection, also the cellular phenotypes and metabolism of the host changes (3), presumably in response to Ascaris E/S products, with oxidative stress products being found in urine (4) and gastrointestinal tract (5) of patients infected with A. lumbricoides. Still, several questions regarding the metabolism as a possible therapeutic target remain elusive: (i) How do the helminths adapt their metabolism to tissue environment for long-term survival? and ii) How does the host metabolism respond to metabolic changes in parasites, with impact on cell phenotypes and functions? We previously focused on the metabolism depending on the coenzymes NADH and NADPH and developed an enzyme-specific reference system for NAD(P)H fluorescence lifetime imaging [NAD(P)H-FLIM (6)] to study metabolic pathways in mammal tissues, in health and diseases (7,8). Further, we adapted our enzyme reference system to monitor the metabolism of Heligmosomoides bakeri, a murine nematode. We showed (i) that H. bakeri adapts its bioenergetics to migrate through the host gut (9); (ii) the cross-talk between parasite and host metabolism, with increased NADPH-dependent oxidative burst in both species (9); (iii) the host microbiome does not impact either adult nematode or host metabolism, and nematodes do not use a Dual oxidase (DUOX)2-dependent oxidative burst against the microbiota (10) or kin nematodes. We adapted the method to A. suum and found a zonal metabolic segregation in the L3 larvae, and negligible impact of artemisinin on their metabolism (11).

On this basis, we aim for DR1 to clarify the dependence of ascarids active NAD(P)H metabolic pathways on the life cycle stage, (tissue) environment and infection load and to assess whether the three ascarid species A. lumbricoides, A. suum and A. galli share a common metabolic behavior. For DR2 we aim to assess which NAD(P)H-dependent metabolic changes take place in the intestinal compartments (epithelial vs. immune, especially myeloid subsets) in pigs and hens, compared to liver and lung and how these affect myeloid functions. A similar analysis will be performed on human blood-derived monocytes, in Ascaris infection.

References:
1) Parvatham et al. 2013, doi: 10.1007/s12257-012-0390-x; 2) Müller et al. 2012, doi: 10.1128/MMBR.05024-11; 3) Midha et al. 2021a, doi: 10.1016/j.pt.2020.09.002; 4) Chandramathi et al. 2010, doi: 10.1017/S0031182009991351; 5) Kilic et al. 2003, doi: 10.3748/wjg.v9.i10.2332; 6) Leben, R. et al. 2019, doi: 10.3390/ijms20225565; 7) Ulbricht et al. 2021, doi: 10.7554/eLife.56020; 8) Lindquist et al.
2018, doi: 10.3390/ijms19051365; 9) Liublin et al. 2022, doi: 10.1038/s41598-022-10705-y. 10) Elizalde-Velázquez et al.2023; doi: 10.1111/pim.12957; 11) Musimbi et al. 2024, doi: 10.1101/2024.08.30.610452.