Posted by Kasra
It is always pleasant to read papers published by friends and old colleagues. Also it was about time I would write another post about Leishmania. This new paper published in Cell host and microbe (pubmed index) discusses a new mechanism that Leishmania parasites use to evade the host immunity.
A quick reminder, the promastigote forms of Leishmania enter the mammalian host via bite of the sandfly. They are readily phagocytosed by macrophages. Yet, they manage to evade to propagate within the macrophage thanks to multiple mechanisms of immune modulation and evasion.
Previous publications of this group that showed how Leishmania is able to impair maturation of the phagolysosome (for example delay acidification) by interfering with phagolysosome associated proteins. Their previous work had pointed to Leishmania‘s surface lipophosphoglycan LPG. Following their work on the phagosome, they look to see if there are other molecules that are also altered after Leishmania infection, stumbling upon VAMP3 and VAMP8, two SNAREs that are cleaved after infection. They find that this time this time this cleavage is due to another important virulence factor of Leishmania namely surface protease GP63. This protease has been shown to have many immunomodulatory properties and cleaving many important macrophage proteins (phosphatases, transcription factors…) and now there is a new one on the list. The authors show that VAMP8 is important for cross-presentation of antigens from MHCII to MHCI. To show this they create ovalbumin expressing expressing L. major and see how presence or absence of GP63 could affect activation of OT-II (ovalbumin-reactive T cells) after coculture with macrophages. Importance of VAMP8 in cross presentation is also shown by using VAMP8-/- cells.
What is nice about this study is that by studying host-parasite interactions and immune modulation, it also helps us learn more about the innate immune mechanisms and communication of the innate and adaptive immune systems.
Matheoud D, Moradin N, Bellemare-Pelletier A, Shio MT, Hong WJ, Olivier M, Gagnon E, Desjardins M, & Descoteaux A (2013). Leishmania Evades Host Immunity by Inhibiting Antigen Cross-Presentation through Direct Cleavage of the SNARE VAMP8. Cell host & microbe, 14 (1), 15-25 PMID: 23870310
Olivier M, Atayde VD, Isnard A, Hassani K, & Shio MT (2012). Leishmania virulence factors: focus on the metalloprotease GP63. Microbes and infection / Institut Pasteur, 14 (15), 1377-89 PMID: 22683718