temperature-induced protein secretion by leishmania mexicana modulates macrophage signalling and function温度引起的蛋白质分泌由利什曼虫墨西哥调节巨噬细胞信号和功能.pdf

Temperature-Induced Protein Secretion by Leishmania mexicana Modulates Macrophage Signalling and Function 1,2 1 3 1,2 Kasra Hassani , Elisabeth Antoniak , Armando Jardim , Martin Olivier * ´ ´ ´ 1 Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada, 2 The Research Institute of the McGill University Health Center, Montreal, ´ ´ ´ Quebec, Canada, 3 Institute of Parasitology, McGill University, Montreal, Quebec, Canada Abstract Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. These digenetic microorganisms undergo a marked environmental temperature shift (TS) during transmission from the sandfly vector (ambient temperature, 25–26uC) to the mammalian host (37uC). We have observed that this TS induces a rapid and dramatic increase in protein release from Leishmania mexicana (cutaneous leishmaniasis) within 4 h. Proteomic identification of the TS-induced secreted proteins revealed 72 proteins, the majority of which lack a signal peptide and are thus thought to be secreted via nonconventional mechanisms. Interestingly, this protein release is accompanied by alterations in parasite morphology including an augmentation in the budding of exovesicles from its surface. Here we show that the exoproteome of L. mexicana upon TS induces cleavage and activation of the host protein tyrosine phosphatases, specifically SHP-1 and PTP1-B, in a murine bone-marrow-der