Leishmania evades host immunity by inhibiting antigen cross-presentation through direct cleavage of the SNARE VAMP8. - Archive ouverte HAL Access content directly
Journal Articles Cell Host and Microbe Year : 2013

Leishmania evades host immunity by inhibiting antigen cross-presentation through direct cleavage of the SNARE VAMP8.

(1) , (2) , (3) , (4) , (5, 6) , (4) , (3) , (1) , (2)
1
2
3
4
5
6

Abstract

During phagocytosis, microorganisms are taken up by immune cells into phagosomes. Through membrane-trafficking events mediated by SNARE proteins, phagosomes fuse with lysosomes, generating degradative phagolysosomes. Phagolysosomes contribute to host immunity by linking microbial killing within these organelles with antigen processing for presentation on MHC class I or II molecules to T cells. We show that the intracellular parasite Leishmania evades immune recognition by inhibiting phagolysosome biogenesis. The Leishmania cell surface metalloprotease GP63 cleaves a subset of SNAREs, including VAMP8. GP63-mediated VAMP8 inactivation or Vamp8 disruption prevents the NADPH oxidase complex from assembling on phagosomes, thus altering their pH and degradative properties. Consequently, the presentation of exogenous Leishmania antigens on MHC class I molecules, also known as cross-presentation, is inhibited, resulting in reduced T cell activation. These findings indicate that Leishmania subverts immune recognition by altering phagosome function and highlight the importance of VAMP8 in phagosome biogenesis and antigen cross-presentation.

Dates and versions

pasteur-01131970 , version 1 (16-03-2015)

Identifiers

Cite

Diana Matheoud, Neda Moradin, Angélique Bellemare-Pelletier, Marina Tiemi Shio, Wan Jin Hong, et al.. Leishmania evades host immunity by inhibiting antigen cross-presentation through direct cleavage of the SNARE VAMP8.. Cell Host and Microbe, 2013, 14 (1), pp.15-25. ⟨10.1016/j.chom.2013.06.003⟩. ⟨pasteur-01131970⟩

Collections

RIIP INRS-IAF
34 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More