Posted by Issa Abu-Dayyeh
I will hereby post the author summary of my most recent publication regarding modulation of macrophage signaling by the Leishmania parasite. The paper has been published on the 23rd of December 2008 in the Public Library of Science (PLoS) Neglected Tropical Diseases, and demonstrates for the first time the ability of Leishmania to inactivate IRAK-1 through its ability to activate host PTP-SHP-1.
Citation: Abu-Dayyeh I, Shio MT, Sato S, Akira S, Cousineau B, et al. (2008) Leishmania-Induced IRAK-1 Inactivation Is Mediated by SHP-1 Interacting with an Evolutionarily Conserved KTIM Motif. PLoS Negl Trop Dis 2(12): e305. doi:10.1371/journal.pntd.0000305
Here is the author summary of the paper:
Leishmania developed several methods to seize control of macrophage signalling pathways in an effort to inactivate their killing abilities. One effective method utilized by the parasite is the activation of host protein tyrosine phosphatases, specifically SHP-1. This increased phosphatase activity contributes to the inactivation of signalling molecules involved in critical macrophage functions such as NO and cytokine production. Interestingly, the absence of SHP-1 results in stronger macrophage inflammatory responses to a bacterial cell wall component known as LPS, a molecule detected by macrophages through Toll-like receptors (TLRs). This observation suggested a role for SHP-1 in the regulation of TLR signalling. Our study reveals that upon Leishmania infection, SHP-1 is able to rapidly bind to and inactivate a critical kinase (IRAK-1) in this pathway. This regulatory binding was shown to be mediated by an evolutionarily conserved motif identified in the kinase. This motif was also present in other kinases involved in Toll signalling and therefore could represent a regulatory mechanism of relevance to many kinases. This work not only reports a unique mechanism by which Leishmania can avoid harmful TLR signalling, but also provides a platform on which extensive investigation on host evasion mechanisms and regulation of cellular kinases can be gained.
For further information please check the citation below to read the whole paper. PLoS is an open-access journal and therefore offers free access to its contents to anybody anywhere in the world!
P.S.: Abstract translations are also available in the following languages: Arabic, French, Spanish, and Farsi.