The host mTOR pathway and parasitic diseases pathogenesis

Parasitol Res. 2021 Apr;120(4):1151-1166. doi: 10.1007/s00436-021-07070-6. Epub 2021 Feb 3.

Abstract

The mechanistic (or mammalian) target of rapamycin (mTOR) is considered as a critical regulatory enzyme involved in essential signaling pathways affecting cell growth, cell proliferation, protein translation, regulation of cellular metabolism, and cytoskeletal structure. Also, mTOR signaling has crucial roles in cell homeostasis via processes such as autophagy. Autophagy prevents many pathogen infections and is involved on immunosurveillance and pathogenesis. Immune responses and autophagy are therefore key host responses and both are linked by complex mTOR regulatory mechanisms. In recent years, the mTOR pathway has been highlighted in different diseases such as diabetes, cancer, and infectious and parasitic diseases including leishmaniasis, toxoplasmosis, and malaria. The current review underlines the implications of mTOR signals and intricate networks on pathogen infections and the modulation of this master regulator by parasites. Parasitic infections are able to induce dynamic metabolic reprogramming leading to mTOR alterations in spite of many other ways impacting this regulatory network. Accordingly, the identification of parasite effects and interactions over such a complex modulation might reveal novel information regarding the biology of the abovementioned parasites and might allow the development of therapeutic strategies against parasitic diseases. In this sense, the effects of inhibiting the mTOR pathways are also considered in this context in the light of their potential for the prevention and treatment of parasitic diseases.

Keywords: Modulation,; Parasites; Rapamycin; Signaling; Therapies; mTOR.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Humans
  • Immunity / drug effects
  • Leishmaniasis / drug therapy
  • Leishmaniasis / parasitology
  • Leishmaniasis / prevention & control
  • Malaria / drug therapy
  • Malaria / parasitology
  • Malaria / prevention & control
  • Parasites / drug effects*
  • Parasites / physiology
  • Parasitic Diseases / drug therapy*
  • Parasitic Diseases / parasitology
  • Parasitic Diseases / prevention & control
  • Phosphorylation
  • Protein Biosynthesis / drug effects
  • Signal Transduction / drug effects*
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / genetics
  • Toxoplasmosis / drug therapy
  • Toxoplasmosis / parasitology
  • Toxoplasmosis / prevention & control

Substances

  • TOR Serine-Threonine Kinases
  • Sirolimus