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Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine

Nasal mucosal tissues are equipped with physical barriers, mucus and cilia, on their surface. The mucus layer captures inhaled materials, and the cilia remove the inhaled materials from the epithelial layer by asymmetrical beating. The effect of nasal physical barriers on the vaccine efficacy remain...

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Autores principales: Lan, Huangwenxian, Suzuki, Hidehiko, Nagatake, Takahiro, Hosomi, Koji, Ikegami, Koji, Setou, Mitsutoshi, Kunisawa, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262165/
https://www.ncbi.nlm.nih.gov/pubmed/32347929
http://dx.doi.org/10.1093/intimm/dxaa029
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author Lan, Huangwenxian
Suzuki, Hidehiko
Nagatake, Takahiro
Hosomi, Koji
Ikegami, Koji
Setou, Mitsutoshi
Kunisawa, Jun
author_facet Lan, Huangwenxian
Suzuki, Hidehiko
Nagatake, Takahiro
Hosomi, Koji
Ikegami, Koji
Setou, Mitsutoshi
Kunisawa, Jun
author_sort Lan, Huangwenxian
collection PubMed
description Nasal mucosal tissues are equipped with physical barriers, mucus and cilia, on their surface. The mucus layer captures inhaled materials, and the cilia remove the inhaled materials from the epithelial layer by asymmetrical beating. The effect of nasal physical barriers on the vaccine efficacy remains to be investigated. Tubulin tyrosine ligase-like family, member 1 (Ttll1) is an essential enzyme for appropriate movement of the cilia on respiratory epithelium, and its deficiency (Ttll1-KO) leads to mucus accumulation in the nasal cavity. Here, when mice were intra-nasally immunized with pneumococcal surface protein A (PspA, as vaccine antigen) together with cholera toxin (CT, as mucosal adjuvant), Ttll1-KO mice showed higher levels of PspA-specific IgA in the nasal wash and increased numbers of PspA-specific IgA-producing plasma cells in the nasal passages when compared with Ttll1 hetero (He) mice. Mucus removal by N-acetylcysteine did not affect the enhanced immune responses in Ttll1-KO mice versus Ttll1-He mice. Immunohistological and flow cytometry analyses revealed that retention time of PspA in the nasal cavity in Ttll1-KO mice was longer than that in Ttll1-He mice. Consistently, uptake of PspA by dendritic cells was higher in the nasopharynx-associated lymphoid tissue (NALT) of Ttll1-KO mice than that of Ttll1-He mice. These results indicate that the ciliary function of removing vaccine antigen from the NALT epithelial layer is a critical determinant of the efficacy of nasal vaccine.
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spelling pubmed-92621652022-07-08 Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine Lan, Huangwenxian Suzuki, Hidehiko Nagatake, Takahiro Hosomi, Koji Ikegami, Koji Setou, Mitsutoshi Kunisawa, Jun Int Immunol Original Research Nasal mucosal tissues are equipped with physical barriers, mucus and cilia, on their surface. The mucus layer captures inhaled materials, and the cilia remove the inhaled materials from the epithelial layer by asymmetrical beating. The effect of nasal physical barriers on the vaccine efficacy remains to be investigated. Tubulin tyrosine ligase-like family, member 1 (Ttll1) is an essential enzyme for appropriate movement of the cilia on respiratory epithelium, and its deficiency (Ttll1-KO) leads to mucus accumulation in the nasal cavity. Here, when mice were intra-nasally immunized with pneumococcal surface protein A (PspA, as vaccine antigen) together with cholera toxin (CT, as mucosal adjuvant), Ttll1-KO mice showed higher levels of PspA-specific IgA in the nasal wash and increased numbers of PspA-specific IgA-producing plasma cells in the nasal passages when compared with Ttll1 hetero (He) mice. Mucus removal by N-acetylcysteine did not affect the enhanced immune responses in Ttll1-KO mice versus Ttll1-He mice. Immunohistological and flow cytometry analyses revealed that retention time of PspA in the nasal cavity in Ttll1-KO mice was longer than that in Ttll1-He mice. Consistently, uptake of PspA by dendritic cells was higher in the nasopharynx-associated lymphoid tissue (NALT) of Ttll1-KO mice than that of Ttll1-He mice. These results indicate that the ciliary function of removing vaccine antigen from the NALT epithelial layer is a critical determinant of the efficacy of nasal vaccine. Oxford University Press 2020-04-29 /pmc/articles/PMC9262165/ /pubmed/32347929 http://dx.doi.org/10.1093/intimm/dxaa029 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Society for Immunology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Lan, Huangwenxian
Suzuki, Hidehiko
Nagatake, Takahiro
Hosomi, Koji
Ikegami, Koji
Setou, Mitsutoshi
Kunisawa, Jun
Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine
title Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine
title_full Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine
title_fullStr Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine
title_full_unstemmed Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine
title_short Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine
title_sort impaired mucociliary motility enhances antigen-specific nasal iga immune responses to a cholera toxin-based nasal vaccine
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262165/
https://www.ncbi.nlm.nih.gov/pubmed/32347929
http://dx.doi.org/10.1093/intimm/dxaa029
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