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

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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Matheoud D,Moradin N,Bellemare-Pelletier A,Shio MT,Hong WJ,Olivier M,Gagnon E,Desjardins M,Descoteaux A

doi

10.1016/j.chom.2013.06.003

subject

Has Abstract

pub_date

2013-07-17 00:00:00

pages

15-25

issue

1

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(13)00219-9

journal_volume

14

pub_type

杂志文章

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