Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences
CpG-oligodeoxynucleotides (CpG-ODNs) mimicking the function of microbial CpG-dideoxynucleotides containing DNA (CpG-DNA) are potent immune stimuli. The immunostimulatory activity and the species-specific activities of a CpG-ODN depend on its nucleotide sequence properties, including CpG-hexamer moti...
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MDPI AG
2020-11-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/4/639 |
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| author | Yu-Chen Chuang Jen-Chih Tseng Jing-Xing Yang Yi-Ling Liu Da-Wei Yeh Chao-Yang Lai Guann-Yi Yu Li-Chung Hsu Chun-Ming Huang Tsung-Hsien Chuang |
| author_facet | Yu-Chen Chuang Jen-Chih Tseng Jing-Xing Yang Yi-Ling Liu Da-Wei Yeh Chao-Yang Lai Guann-Yi Yu Li-Chung Hsu Chun-Ming Huang Tsung-Hsien Chuang |
| author_sort | Yu-Chen Chuang |
| collection | DOAJ |
| description | CpG-oligodeoxynucleotides (CpG-ODNs) mimicking the function of microbial CpG-dideoxynucleotides containing DNA (CpG-DNA) are potent immune stimuli. The immunostimulatory activity and the species-specific activities of a CpG-ODN depend on its nucleotide sequence properties, including CpG-hexamer motif types, spacing between motifs, nucleotide sequence, and length. Toll-like receptor (TLR) 9 is the cellular receptor for CpG-ODNs in mammalian species, while TLR21 is the receptor in avian species. Mammalian cells lack TLR21, and avian cells lack TLR9; however, both TLRs are expressed in fish cells. While nucleotide sequence properties required for a CpG-ODN to strongly activate mammalian TLR9 and its species-specific activities to different mammalian TLR9s are better studied, CpG-ODN activation of TLR21 is not yet well investigated. Here we characterized chicken and duck TLR21s and investigated their activation by CpG-ODNs. Chicken and duck TLR21s contain 972 and 976 amino acid residues, respectively, and differ from TLR9s as they do not have an undefined region in their ectodomain. Cell-based TLR21 activation assays were established to investigate TLR21 activation by different CpG-ODNs. Unlike grouper TLR21, which was preferentially activated by CpG-ODN with a GTCGTT hexamer motif, chicken and duck TLR21s do not distinguish among different CpG-hexamer motifs. Additionally, these two poultry TLR21s were activated by CpG-ODNs with lengths ranging from 15 to 31 nucleotides and with different spacing between CpG-hexamer motifs. These suggested that compared to mammalian TLR9 and grouper TLR21, chicken and duck TLR21s have a broad CpG-ODN sequence recognition profile. Thus, they could also recognize a wide array of DNA-associated molecular patterns from microbes. Moreover, CpG-ODNs are being investigated as antimicrobial agents and as vaccine adjuvants for different species. This study revealed that there are more optimized CpG-ODNs that can be used in poultry farming as anti-infection agents compared to CpG-ODN choices available for other species. |
| first_indexed | 2024-03-10T15:09:13Z |
| format | Article |
| id | doaj.art-913b337f664b41e799966733253da2b3 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T15:09:13Z |
| publishDate | 2020-11-01 |
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| series | Vaccines |
| spelling | doaj.art-913b337f664b41e799966733253da2b32023-11-20T19:30:56ZengMDPI AGVaccines2076-393X2020-11-018463910.3390/vaccines8040639Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide SequencesYu-Chen Chuang0Jen-Chih Tseng1Jing-Xing Yang2Yi-Ling Liu3Da-Wei Yeh4Chao-Yang Lai5Guann-Yi Yu6Li-Chung Hsu7Chun-Ming Huang8Tsung-Hsien Chuang9Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, TaiwanImmunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, TaiwanImmunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, TaiwanImmunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, TaiwanImmunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, TaiwanDepartment of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, TaiwanInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10002, TaiwanDepartment of Biomedical Sciences and Engineering, National Central University, Taoyuan 32001, TaiwanImmunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, TaiwanCpG-oligodeoxynucleotides (CpG-ODNs) mimicking the function of microbial CpG-dideoxynucleotides containing DNA (CpG-DNA) are potent immune stimuli. The immunostimulatory activity and the species-specific activities of a CpG-ODN depend on its nucleotide sequence properties, including CpG-hexamer motif types, spacing between motifs, nucleotide sequence, and length. Toll-like receptor (TLR) 9 is the cellular receptor for CpG-ODNs in mammalian species, while TLR21 is the receptor in avian species. Mammalian cells lack TLR21, and avian cells lack TLR9; however, both TLRs are expressed in fish cells. While nucleotide sequence properties required for a CpG-ODN to strongly activate mammalian TLR9 and its species-specific activities to different mammalian TLR9s are better studied, CpG-ODN activation of TLR21 is not yet well investigated. Here we characterized chicken and duck TLR21s and investigated their activation by CpG-ODNs. Chicken and duck TLR21s contain 972 and 976 amino acid residues, respectively, and differ from TLR9s as they do not have an undefined region in their ectodomain. Cell-based TLR21 activation assays were established to investigate TLR21 activation by different CpG-ODNs. Unlike grouper TLR21, which was preferentially activated by CpG-ODN with a GTCGTT hexamer motif, chicken and duck TLR21s do not distinguish among different CpG-hexamer motifs. Additionally, these two poultry TLR21s were activated by CpG-ODNs with lengths ranging from 15 to 31 nucleotides and with different spacing between CpG-hexamer motifs. These suggested that compared to mammalian TLR9 and grouper TLR21, chicken and duck TLR21s have a broad CpG-ODN sequence recognition profile. Thus, they could also recognize a wide array of DNA-associated molecular patterns from microbes. Moreover, CpG-ODNs are being investigated as antimicrobial agents and as vaccine adjuvants for different species. This study revealed that there are more optimized CpG-ODNs that can be used in poultry farming as anti-infection agents compared to CpG-ODN choices available for other species.https://www.mdpi.com/2076-393X/8/4/639adjuvantimmune modulatorinnate immunitytoll-like receptorvaccine |
| spellingShingle | Yu-Chen Chuang Jen-Chih Tseng Jing-Xing Yang Yi-Ling Liu Da-Wei Yeh Chao-Yang Lai Guann-Yi Yu Li-Chung Hsu Chun-Ming Huang Tsung-Hsien Chuang Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences Vaccines adjuvant immune modulator innate immunity toll-like receptor vaccine |
| title | Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences |
| title_full | Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences |
| title_fullStr | Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences |
| title_full_unstemmed | Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences |
| title_short | Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences |
| title_sort | toll like receptor 21 of chicken and duck recognize a broad array of immunostimulatory cpg oligodeoxynucleotide sequences |
| topic | adjuvant immune modulator innate immunity toll-like receptor vaccine |
| url | https://www.mdpi.com/2076-393X/8/4/639 |
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