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Immunometabolic Circuits in Infection for Advancing Host Directed Therapies
Published on: September 13, 2024
The host mTOR pathway and parasitic diseases pathogenesis
Sajad Rashidi1, Reza Mansouri2, Mohammad Ali-Hassanzadeh3
1Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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.
Insights
The mechanistic target of rapamycin (mTOR) pathway regulates cell functions and immunity. Parasites can alter mTOR signaling, offering new therapeutic targets for parasitic diseases.
Area of Science:
- Cell Biology
- Immunology
- Parasitology
Background:
- The mechanistic target of rapamycin (mTOR) is a key regulator of cell growth, metabolism, and homeostasis.
- mTOR signaling is intricately linked with autophagy and immune responses.
- Dysregulation of mTOR is implicated in various diseases, including cancer and diabetes.
Purpose of the Study:
- To review the role of mTOR signaling in host-pathogen interactions, particularly in parasitic infections.
- To explore how parasites modulate the mTOR pathway.
- To discuss the therapeutic potential of targeting mTOR in parasitic diseases.
Main Methods:
- Literature review of studies on mTOR signaling, autophagy, and parasitic infections.
- Analysis of mechanisms by which parasites interact with the mTOR pathway.
- Examination of the effects of mTOR inhibition in the context of parasitic diseases.
Main Results:
- Parasitic infections can induce significant metabolic reprogramming, leading to alterations in mTOR signaling.
- Parasites employ diverse strategies to modulate the host's mTOR network.
- mTOR pathway modulation by parasites impacts host immunity and pathogenesis.
- Inhibiting mTOR shows potential for preventing and treating parasitic diseases.
Conclusions:
- mTOR signaling is a critical nexus in host-parasite interactions.
- Understanding parasite-induced mTOR alterations can reveal parasite biology.
- Targeting mTOR represents a promising therapeutic avenue for combating parasitic infections.
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