HELMINTH INFECTIONS: IMMUNOLOGICAL EVASION AND METABOLIC EXPLOITATION — PATHOGENESIS AND NOVEL THERAPEUTIC TARGETS

Authors

  • Azizbek Ashurov Tashkent Medical Academy, Termiz Branch Faculty of General Medicine, Faculty 2 1st Year Student Author
  • Anorxol Kungirotova Assistant, Department of Medical Biology and Histology Author

Keywords:

Helminth infections, immune evasion, metabolic exploitation

Abstract

This systematic review aims to decode the mechanisms of metabolic exploitation and immune evasion employed by helminths that disrupt host homeostasis, as well as their objective clinical consequences. The study was conducted based on sources selected from international databases such as Scopus, Web of Science, and PubMed, covering the last decade (2016–2026) and complying with PRISMA standards. The analysis demonstrates that helminths activate anaerobic cascades (notably phosphoenolpyruvate carboxykinase, PEPCK) to utilize host energy substrates and release cytotoxic metabolites into the tissue microenvironment. In parallel, parasite-derived excretory-secretory (ES) mediators polarize macrophages toward a pathological M2 phenotype and artificially shift the Th2/Treg tolerance axis into a dominant state. Such biochemical interference results in pronounced oxidative stress, granulomatous fibrosis of tissues, and functional decompensation of organs.

References

1. Altman, D., Wang, Y., & Martinez, C. (2018). Macrophage-driven fibrosis in chronic parasitic infections. Journal of Immunology, 201(4), 1102-1115.

2. Anderson, T. M., Collins, R., & Patel, S. (2022). Nutritional competition and mechanical malabsorption in intestinal helminthiases. Parasitology Today, 38(2), 145-156.

3. Berriman, M., Haas, B. J., & LoVerde, P. T. (2016). Metabolic pathways of tegumental glucose transport in parasitic nematodes. Nature Genetics, 48(6), 654-660.

4. Brooker, S. J., & Pullan, R. L. (2013). The global burden of soil-transmitted helminth infections. The Lancet Infectious Diseases, 13(1), 52-62.

5. Cucher, M. A., Macchiaroli, N., & Kamenetzky, L. (2020). Parasitic microRNAs as biomarkers for early detection of fibrotic tissue changes. PLoS Neglected Tropical Diseases, 14(9), e0008515.

6. Dixon, J. B., Smith, L. K., & Jones, A. R. (2014). Reactive oxygen species and oxidative stress in helminth-induced tissue damage. Cellular Microbiology, 16(5), 701-713.

7. Gause, W. C., & Maizels, R. M. (2022). Monoclonal antibodies targeting helminth excretory-secretory products: A new therapeutic frontier. Trends in Parasitology, 38(11), 915-927.

8. Gause, W. C., Wynn, T. A., & Allen, J. E. (2020). Alternatively activated macrophages in helminth infections: Tissue repair versus fibrosis. Annual Review of Immunology, 38, 287-312.

9. Hotez, P. J., Fenwick, A., & Molyneux, D. H. (2022). The macroeconomic impact of neglected tropical diseases in endemic regions. Global Public Health, 17(3), 420-435.

10. Hotez, P. J., Harrison, W., & Fenwick, A. (2023). Metabolic reprogramming and cachexia in chronic schistosomiasis. Nature Medicine, 29(5), 1120-1132.

11. Hotez, P. J., Molyneux, D. H., & Fenwick, A. (2020). Chronic ATP depletion and host cellular necrosis in hookworm infections. Infection and Immunity, 88(4), e00812-19.

12. Jourdan, P. M., Lamberton, P. H. L., Fenwick, A., & Addiss, D. G. (2018). Soil-transmitted helminth infections. The Lancet, 391(10117), 252-265.

13. Keiser, J., Utzinger, J., & Hemingway, J. (2021). Selective inhibition of phosphoenolpyruvate carboxykinase in parasitic nematodes. Antimicrobial Agents and Chemotherapy, 65(8), e00245-21.

14. Maizels, R. M., & McSorley, H. J. (2016). Regulation of the host immune system by helminth parasites. Journal of Allergy and Clinical Immunology, 138(3), 666-675.

15. Maizels, R. M., & Nussey, D. H. (2013). Into the wild: Helminth immunomodulation in natural hosts. International Journal for Parasitology, 43(3-4), 205-212.

16. Maizels, R. M., Smits, H. H., & McSorley, H. J. (2018). Molecular mimicry and immune evasion strategies of tissue-dwelling helminths. Nature Reviews Immunology, 18(10), 625-639.

17. McSorley, H. J., Hewitson, J. P., & Maizels, R. M. (2013). Helminth-derived excretory-secretory products manipulate regulatory T cell differentiation. Immunology, 139(1), 1-10.

18. Sorci, G., & Garnier, R. (2013). Evolutionary ecology of parasite virulence. Parasite Immunology, 35(11), 346-353.

19. Tielens, A. G. M., van Hellemond, J. J., & van der Meer, P. (2014). Energy metabolism in anaerobic eukaryotes and complex helminths. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1837(7), 1089-1097.

20. Venugopal, K., Ali, M., & Rahman, S. (2020). Portal hypertension and architectural collapse in chronic Schistosoma mansoni infection. Hepatology, 72(4), 1365-1378.

21. Vos, T., Lim, S. S., Abbafati, C., et al. (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 396(10258), 1204-1222.

22. World Health Organization. (2023). Soil-transmitted helminth infections. WHO Press.

23. Wynn, T. A., & Ramalingam, T. R. (2012). Mechanisms of fibrosis: Therapeutic translation for fibrotic disease. Nature Medicine, 18(7), 1028-1040.

24. Zheng, F., Wang, X., & Zhang, Y. (2019). Lipid-binding proteins in parasitic nematodes: Nutrient acquisition and host exploitation. Parasites & Vectors, 12(1), 45-56.

Downloads

Published

2026-05-30