PMID- 36159835
OWN - NLM
STAT- MEDLINE
DCOM- 20220928
LR  - 20221003
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Delivery of antigen to porcine dendritic cells by fusing antigen with porcine 
      dendritic cells targeting peptide.
PG  - 926279
LID - 10.3389/fimmu.2022.926279 [doi]
LID - 926279
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that can 
      recognize, capture, and process antigens. Fusing molecules targeting DCs with 
      antigens can effectively improve the efficiency with which antigens are 
      recognized and captured by DCs. This targeting strategy can be used for vaccine 
      development to effectively improve the efficiency of antigen recognition and 
      capture by DCs. The targeting sequence of porcine cytotoxic T-lymphocyte 
      associated protein 4 (CTLA4), which binds porcine DCs, was identified in this 
      study. Recombinant Lactobacillus reuteri (L. reuteri) expressing CTLA4-6aa 
      (LYPPPY) and CTLA4-87aa fused to the porcine epidemic diarrhea virus (PEDV) 
      protective antigen core neutralizing epitope (COE) were used to evaluate the 
      ability of the two targeting motifs to bind the B7 molecule on DCs. Our results 
      demonstrate that CTLA4-6aa could bind porcine DCs, and recombinant Lactobacillus 
      expressing the CTLA4-6aa captured by porcine DCs was more efficient than those 
      expressing CTLA4-87aa. In addition, the expression of DC markers, toll-like 
      receptors, and cytokines was significantly higher in the 6aa-COE/L. 
      reuteri-stimulated porcine DCs compared to DCs treated with 87aa-COE/L. reuteri 
      (p<0.01) and recombinant Lactobacillus expressing CTLA4-6aa enhanced the ability 
      of porcine DCs to activate T-cell proliferation. Our analysis of the protein 
      structure revealed that CTLA4-87aa contains intramolecular hydrogen bonds, which 
      may have weakened the intermolecular force between the residues on porcine CTLA4 
      and that on B7. In conclusion, recombinant Lactobacillus expressing CTLA4-6aa 
      were more efficiently captured by porcine DCs and had a stronger ability to 
      promote DC maturation and enhance T-cell proliferation. The LYPPPY motif is the 
      optimal sequence for binding to porcine DCs. Piglets immunized with recombinant 
      Lactobacillus showed that recombinant Lactobacillus expressing CTLA4-6aa induced 
      significant levels of anti-PEDV-specific IgG and IgA antibody responses. Our 
      study may promote research on DC-targeting strategies to enhance the 
      effectiveness of porcine vaccines.
CI  - Copyright (c) 2022 Xia, Wang, Tang, Gao, Gao, Hao, Jiang, Wang, Shan, Li, Zhou, 
      Cui, Qiao, Tang, Wang and Li.
FAU - Xia, Tian
AU  - Xia T
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Wang, Ning
AU  - Wang N
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Tang, Yuqing
AU  - Tang Y
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Gao, Yueyi
AU  - Gao Y
AD  - Division of Viral Biologic Testing(I), China Institute of Veterinary Drug 
      Control, Beijing, China.
FAU - Gao, Chong
AU  - Gao C
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Hao, Jianhui
AU  - Hao J
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Jiang, Yanping
AU  - Jiang Y
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Wang, Xiaona
AU  - Wang X
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Shan, Zhifu
AU  - Shan Z
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Li, Jiaxuan
AU  - Li J
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Zhou, Han
AU  - Zhou H
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Cui, Wen
AU  - Cui W
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Qiao, Xinyuan
AU  - Qiao X
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Tang, Lijie
AU  - Tang L
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Wang, Li
AU  - Wang L
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
FAU - Li, Yijing
AU  - Li Y
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, 
      Northeastern Science Inspection Station, Harbin, China.
LA  - eng
PT  - Journal Article
DEP - 20220908
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (B7 Antigens)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Cytokines)
RN  - 0 (Epitopes)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptides)
SB  - IM
MH  - Animals
MH  - B7 Antigens
MH  - CTLA-4 Antigen
MH  - Cytokines
MH  - *Dendritic Cells
MH  - Epitopes
MH  - Immunoglobulin A
MH  - Immunoglobulin G
MH  - Lactobacillus
MH  - Peptides
MH  - Swine
PMC - PMC9499840
OTO - NOTNLM
OT  - CTLA4
OT  - fusion expression
OT  - porcine dendritic cells
OT  - recombinant lactobacillus
OT  - targeting
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/09/27 06:00
MHDA- 2022/09/28 06:00
PMCR- 2022/01/01
CRDT- 2022/09/26 17:41
PHST- 2022/05/12 00:00 [received]
PHST- 2022/08/18 00:00 [accepted]
PHST- 2022/09/26 17:41 [entrez]
PHST- 2022/09/27 06:00 [pubmed]
PHST- 2022/09/28 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.926279 [doi]
PST - epublish
SO  - Front Immunol. 2022 Sep 8;13:926279. doi: 10.3389/fimmu.2022.926279. eCollection 
      2022.