<16> Cysteine PeptidaseB Regulates Leishmania mexicana Virulence through the Modulation ofGP63 Expression
Cysteine Peptidase B Regulates Leishmania mexicana Virulence through the Modulation of GP63 Expression
Pierre-André Casgrain , Caroline Martel , W. Robert McMaster , Jeremy C. Mottram4 , Martin Olivier , Albert Descoteaux
PLoS Pathog(2016) 12(5):e100565
Speaker: Po-Liang, Chu (朱珀亮) Time: 15:00~16:00, Oct 26 2016
Commentator: Dr. Wei-Chen, Lin (林威辰 老師) Place: Room 601
Abstract:
Leishmania mexicana is a genus of trypanosomes that are responsible for the disease leishmaniasis. They are spread by sandflies of the genus Lutzomyia in the world. Leishmaniasis include three types in human. Cutaneous leishmaniasis, Mucocutaneous leishmaniasis and Visceral leishmaniasis. Leishmania mexicana cause cutaneous leishmaniasis. Inside macrophages, promastigotes differentiate into amastigotes to replicate within phagolysosomal compartments also known as parasitophorous vacuoles (PVs). Leishmania mexicana expresses several cysteine peptidases of the papain family that are involved in processes such as virulence and evasion of host immune responses. However, it is clear that CPB are important Leishmania virulence factors and potential therapy targets. The authors discovered that expression of the virulence-associated GPI-anchored metalloprotease GP63 was inhibited in the absence of CPB. CPB is required for GP63 expression. During phagocytosis, microorganisms are taken up by immune cells into phagosomes. Through membrane-trafficking events mediated by SNARE proteins, phagosomes fuse with lysosomes. The Leishmania cell surface metalloprotease GP63 cleaves a subset of SNAREs, including VAMP8.[1] In this article, the authors expression of GP63 in the CPB-deficient mutant was sufficient to down-modulate VAMP3 and VAMP8. GP63 is responsible for the cleavage of VAMP3 and VAMP8 by L. Mexicana. Finally, The authors want to assess the impact of GP63 on the ability of Δcpb to cause lesions, they used a mouse model of cutaneous leishmaniasis. Remarkably, expression of GP63 in Δcpb restored its capacity to cause lesions. These findings implicate CPB in the regulation of GP63 expression and provide evidence that both GP63 and CPB are key virulence factors in L. mexicana.
Reference:
1. Matheoud D, Moradin N, Bellemare-Pelletier A, Shio MT, Hong WJ, Olivier M, et al. Leishmania evades host immunity by inhibiting antigen cross-presentation through direct cleavage of the SNARE VAMP8. Cell Host Microbe. 2013; 14: 15–25. doi: 10.1016/j.chom.2013.06.003