PMID- 37736336
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230923
IS  - 2228-5652 (Print)
IS  - 2228-5660 (Electronic)
IS  - 2228-5652 (Linking)
VI  - 13
IP  - 5
DP  - 2023
TI  - Autophagy induced macrophages by alpha-alumina(alpha-AL2O3) conjugated cysteine 
      peptidase, enhances the cytotoxic activity of CD8(+) T lymphocytes against 
      Leishmania major.
PG  - 393-403
LID - 10.34172/bi.2023.25282 [doi]
AB  - INTRODUCTION: Induction of a protective immune response against Leishmania major 
      requires the activation of both TH1 and CD8(+) T lymphocytes. Because L. major is 
      an intra-phagosomal parasite, its antigens do not have access to MHC-I. The 
      present study aimed to evaluate the effect of cysteine peptidase A (CPA)/cysteine 
      peptidase B (CPB) conjugated to alpha-AL2O3 on autophagy induction in L. major 
      infected macrophages and subsequent activation of cytotoxic CD8(+) T lymphocytes. 
      METHODS: Recombinant CPA and CPB of L. major were produced in expression vectors 
      and purified. Aldehyde functionalized alpha-AL2O3 were conjugated to 
      hydrazine-modified CPA/CPB by a chemical bond was confirmed by Fourier-transform 
      infrared spectroscopy (FTIR). The High efficient internalization of alpha-AL2O3 
      conjugated CPA/CPB to macrophages was confirmed using a fluorescence microscope 
      and flowcytometry. Induction of the acidic autophagosome and LC3 conversion in 
      macrophages was determined by acridine orange (AO) staining and western blot. 
      Autophagy-activated macrophages were used for CD8(+) T cell priming. Cytotoxic 
      activity of the primed CD8(+) T cell against L. major infected macrophages was 
      measured using apoptosis assay. RESULTS: alpha-AL2O3 conjugated CPA/CPB enhances 
      macrophages antigen uptake and increases acidic vacuole formation and LC-3I to 
      LC-3II conversion. Co-culture of autophagy-activated macrophages with CD8(+) T 
      cells augmented CD8(+) T cells priming and proliferation more than in other study 
      groups. These primed CD8(+) T cells induce significant apoptotic death of L. 
      major infected macrophages compared with non-primed CD8(+) T cells. CONCLUSION: 
      alpha-AL2O3 nanoparticles enhance the cross-presentation of L. major antigens to 
      CD8(+) T cells by inducing autophagy. This finding supports the positive role of 
      autophagy and encourages the use of alpha-AL2O3 in vaccine design.
CI  - (c) 2023 The Author(s).
FAU - Beyzay, Fatemeh
AU  - Beyzay F
AUID- ORCID: 0000-0001-7599-4757
AD  - Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares 
      University, Tehran, Iran.
FAU - Zavaran Hosseini, Ahmad
AU  - Zavaran Hosseini A
AUID- ORCID: 0000-0002-4078-110X
AD  - Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares 
      University, Tehran, Iran.
FAU - Hazrati, Ali
AU  - Hazrati A
AD  - Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares 
      University, Tehran, Iran.
FAU - Karimi, Mozhdeh
AU  - Karimi M
AD  - Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares 
      University, Tehran, Iran.
FAU - Soudi, Sara
AU  - Soudi S
AUID- ORCID: 0000-0002-8978-3958
AD  - Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares 
      University, Tehran, Iran.
LA  - eng
PT  - Journal Article
DEP - 20230107
PL  - Iran
TA  - Bioimpacts
JT  - BioImpacts : BI
JID - 101558125
PMC - PMC10509742
OTO - NOTNLM
OT  - Autophagy
OT  - Cysteine peptidase
OT  - Cytotoxic T cell
OT  - Leishmania major
OT  - alpha-Alumina
COIS- The authors declare no conflict of interest.
EDAT- 2023/09/22 06:42
MHDA- 2023/09/22 06:43
PMCR- 2023/01/01
CRDT- 2023/09/22 03:44
PHST- 2022/02/20 00:00 [received]
PHST- 2022/08/15 00:00 [revised]
PHST- 2022/08/17 00:00 [accepted]
PHST- 2023/09/22 06:43 [medline]
PHST- 2023/09/22 06:42 [pubmed]
PHST- 2023/09/22 03:44 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.34172/bi.2023.25282 [doi]
PST - ppublish
SO  - Bioimpacts. 2023;13(5):393-403. doi: 10.34172/bi.2023.25282. Epub 2023 Jan 7.