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Apoptotic-like Leishmania exploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination
- Source :
- Autophagy
- Publication Year :
- 2015
- Publisher :
- Taylor & Francis, 2015.
-
Abstract
- Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed--in contrast to viable parasites--that apoptotic-like parasites enter an LC3(+), autophagy-like compartment. The compartment was found to consist of a single lipid bilayer, typical for LC3-associated phagocytosis (LAP). As LAP can provoke anti-inflammatory responses and autophagy modulates antigen presentation, we analyzed how the presence of apoptotic-like parasites affected the adaptive immune response. Macrophages infected with viable Leishmania induced proliferation of CD4(+) T-cells, leading to a reduced intracellular parasite survival. Remarkably, the presence of apoptotic-like parasites in the inoculum significantly reduced T-cell proliferation. Chemical induction of autophagy in human monocyte-derived macrophage (hMDM), infected with viable parasites only, had an even stronger proliferation-reducing effect, indicating that host cell autophagy and not parasite viability limits the T-cell response and enhances parasite survival. Concluding, our data suggest that apoptotic-like Leishmania hijack the host cells' autophagy machinery to reduce T-cell proliferation. Furthermore, the overall population survival is guaranteed, explaining the benefit of apoptosis-like cell death in a single-celled parasite and defining the host autophagy pathway as a potential therapeutic target in treating Leishmaniasis.
- Subjects :
- log.ph, logarithmic phase
T-Lymphocytes
Apoptosis
MACS, magnetic-associated cell sorting
Macrophage
MFI, mean fluorescence intensity
Leishmaniasis
MOI, multiplicity of infection
anti-inflammatory
Leishmania
education.field_of_study
Phagocytes
CFSE, carboxyfluorescein succinimidyl ester
TGFB, transforming growth factor
Acquired immune system
apoptotic-like Leishmania
PS, phosphatidylserine
human primary macrophages
Cell biology
β
TT, tetanus toxoid
Corrigendum
Programmed cell death
autophagy
Population
Antigen presentation
ANXA5, annexin V
Basic Science Research Papers
Biology
Phagocytosis
CM, complete medium
MAP1LC3/LC3, microtubule-associated protein 1 light chain 3
Animals
Humans
MHC, major histocompatibility complex
IF, immunofluorescence
education
Molecular Biology
immune evasion
PBMCs, peripheral blood mononuclear cells
T-cell proliferation
Intracellular parasite
Macrophages
stat.ph, stationary phase
Autophagy
Lm, Leishmania
Cell Biology
biology.organism_classification
IL, interleukin
LAP, LC3-associated phagocytosis
LAP
hMDM, human monocyte derived macrophage
Subjects
Details
- Language :
- English
- ISSN :
- 15548635 and 15548627
- Volume :
- 11
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Autophagy
- Accession number :
- edsair.doi.dedup.....a3d4c51b6d0167edde6a36126fbd4617