Skip to main content

Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Disruption of the AKT/MTOR pathway by Leishmania major promastigotes

Signaling through the Akt/mammalian target of rapamycin (mTOR) pathway plays a pivotal role in the regulation of multiple cellular processes, including proliferation, apoptosis, protein synthesis and autophagy. It is therefore a major target of microbial infections and tumors. Protozoa of the Leishmania genus cause a wide spectrum of diseases in humans, termed leishmaniases, with clinical manifestations ranging from self-healing skin ulcers to life-threatening visceral disease. These parasites primarily infect macrophages and are renowned for their ability to sabotage host-cell signal transduction pathways. Here, we report that infection of Balb/c bone marrow-derived macrophages with the promastigote stage of Leishmania major results in rapid, time-dependent degradation of key components of the Akt/mTOR axis, including Akt, mTOR and the tuberous sclerosis complex-2 (TSC-2). Disruption of the Akt/mTOR pathway by L. major is dependent on the surface metalloprotease gp63, an important virulence factor of the parasite, and appears to be strain- and species-specific. The consequences of the degradation of key intermediates in the Akt/mTOR pathway on downstream responses are currently being investigated. These studies highlight a novel mechanism by which L. major interferes with macrophage functions and responses and will provide a better understanding of Leishmania pathogenesis.

Author information

Correspondence to Christine Matte.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Matte, C., Descoteaux, A. Disruption of the AKT/MTOR pathway by Leishmania major promastigotes. BMC Proc 5, P44 (2011). https://doi.org/10.1186/1753-6561-5-S1-P44

Download citation

Keywords

  • Virulence Factor
  • Tuberous Sclerosis
  • Major Target
  • Microbial Infection
  • Skin Ulcer