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Parasites of the genus Leishmania are able to secure their survival and propagation within their host by altering key signalling pathways involved in the ability of macrophages (MØs) to directly kill pathogens or to activate cells of the adaptive immune system. One important step in this immune evasion process is the Leishmania-induced activation of host protein tyrosine phosphatase SHP-1. SHP-1 has been shown to directly inactivate JAK2 and Erk1/2, and to play a role in the negative regulation of several transcription factors involved in MØ activation such as: NF-κB, STAT-1α, and AP-1. These signalling alterations contribute to the inactivation of critical MØ functions such as the production of IFN-γ-induced nitric oxide (NO), a free radical associated with parasite killing and clearance. In addition to interfering with IFN-γ receptor signalling, Leishmania is able to alter several LPS-mediated responses (e.g. IL-12, TNF-α, NO production) through mechanisms not yet fully understood. A main goal of this study was to better understand the mechanisms used by the parasite to block Toll-like receptor (TLR)-mediated functions. Experiments performed revealed a pivotal role for SHP-1 in the inhibition of TLR-induced MØ activation through binding to and inactivating IL-1 receptor-associated kinase 1 (IRAK-1). We identified the binding site as an evolutionarily conserved ITIM-like motif, which we named kinase tyrosine-based inhibitory motif (KTIM). Further experiments and sequence analysis revealed that several cytosolic kinases other than IRAK-1 possess potential KTIMs, suggesting it could represent a regulatory mechanism widely used by kinases. The final experimental section aimed to explore the differential ability of the two different stages of Leishmania, promastigotes and amastigotes, to alter MØ signalling and function. In conclusion, this work uncovers a new mechanism whereby Leishmania is able to interfere with TLR-mediated activation of MØs by inducing host SHP-1 activity. The SHP-1 binding site on IRAK-1 was named KTIM, a motif we believe might play a major role in regulating a wide range of kinases other than IRAK-1. In addition, we describe important similarities and differences in the ability of promastigotes and amastigotes to alter several MØ signalling molecules in order to inhibit IFN-γ-mediated NO production in MØs. Taken together, the experiments performed in this work are aimed to improve our understanding of evasion mechanisms employed by promastigotes and/or amastigotes of Leishmania, hoping such findings will help in the development of more efficient anti-leishmanial therapies in the near future.