Today : Jan 17, 2025
Science
17 January 2025

Research Reveals Distinct Metabolic Profiles Of A. Suum Larvae And Macrophages

Study highlights unperturbed energy metabolism of parasite larvae contrasted with altered macrophage responses to artemisinin derivatives.

Research findings indicate significant differences in how artemisinin derivatives affect the metabolic processes of the parasitic worm ascaris and host macrophages. Two-photon NAD(P)H fluorescence lifetime imaging (FLIM) reveals insights on energy metabolism of A. suum larvae and porcine macrophages.

The roundworm A. lumbricoides and its zoonotic counterpart A. suum affect millions, causing health issues compounded by co-infections like malaria. Artemisinin derivatives, primarily used for malaria treatment, influence energy metabolism across various cell types.

The study conducted experiments on A. suum larvae and M2-like macrophages, exploiting their bioenergetic profiles under steady-state conditions. Results showed high oxidative phosphorylation (OxPhos) as the main metabolic pathway for both larvae and macrophages.

Interestingly, exposure to artemisinin derivatives led to contrasting effects. The larvae maintained their metabolic profiles with no significant changes detected, as researchers noted, "neither artesunate nor artemether induced a shift in the metabolic profile of the larvae." This indicates resilience to the medications.

Conversely, detached observations depict metabolic shifts within macrophages. Treatment with artesunate led to significant alterations, transitioning the metabolic state from high OxPhos/low anaerobic glycolysis to high OxPhos/high anaerobic glycolysis, emphasizing how immune cells adapt their energy profiles under treatment.

Using NAD(P)H-FLIM, researchers highlighted two distinct metabolically active regions within the larvae—specifically the pharynx and midgut—identified through their differential fluorescence intensity and activity. The pharynx was particularly noted for higher metabolic activity, as it displayed "the pharynx displayed higher overall metabolic activity than the midgut."

Findings could shape future therapeutic directions, especially considering the persistent co-infections of parasites and Plasmodium species. The study highlights the adaptability of macrophage metabolism, potentially implying interactions between host and pathogen mechanisms beyond direct influences of pharmaceuticals.

By advancing methodologies like FLIM for studying live parasite-host metabolic interactions, researchers can expect richer insights on combatting complex infections. This and similar studies set the stage for greater understandings of how specific treatments could alter parasitic life cycles and host immune responses.

Overall, the interplay of artemisinin derivatives on A. suum larvae remains pivotal, demonstrating no adverse metabolic disruptions, yet raising questions about indirect effects on concurrent infections, such as malaria management. The study solidifies the importance of targeted treatments capable of addressing multiple concurrent parasitic infections, promoting comprehensive healthcare strategies to reduce global disease burdens.