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cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue

Induction of immunoglobulin (Ig) A in the mucosa of the upper respiratory tract and the nasal cavity protects against influenza virus infection. Cyclic dinucleotides (CDNs) are used as mucosal adjuvants to enhance the immunogenicity of intranasal influenza hemagglutinin (HA) vaccines. The adjuvant a...

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Autores principales: Takaki, Hiromi, Takashima, Ken, Oshiumi, Hiroyuki, Ainai, Akira, Suzuki, Tadaki, Hasegawa, Hideki, Matsumoto, Misako, Seya, Tsukasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753664/
https://www.ncbi.nlm.nih.gov/pubmed/29258267
http://dx.doi.org/10.3390/medsci5040035
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author Takaki, Hiromi
Takashima, Ken
Oshiumi, Hiroyuki
Ainai, Akira
Suzuki, Tadaki
Hasegawa, Hideki
Matsumoto, Misako
Seya, Tsukasa
author_facet Takaki, Hiromi
Takashima, Ken
Oshiumi, Hiroyuki
Ainai, Akira
Suzuki, Tadaki
Hasegawa, Hideki
Matsumoto, Misako
Seya, Tsukasa
author_sort Takaki, Hiromi
collection PubMed
description Induction of immunoglobulin (Ig) A in the mucosa of the upper respiratory tract and the nasal cavity protects against influenza virus infection. Cyclic dinucleotides (CDNs) are used as mucosal adjuvants to enhance the immunogenicity of intranasal influenza hemagglutinin (HA) vaccines. The adjuvant activity of 2′3′ cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) on Ig production was investigated in nasal-associated lymphoid tissue (NALT), serum of wild-type C57BL/6J, and stimulator of interferon genes (STING)-deficient mice, which do not recognize cGAMP. Mice were vaccinated intranasally with a HA vaccine with or without the cGAMP adjuvant. IgA and IgG production, T-cell responses, germinal center formation, and cytokine expression in NALT were assayed. cGAMP enhanced IgA and IgG production, and promoted T-cell responses. Intranasal administration of cGAMP activated both NALT and systemic immune cells, induced a favorable cytokine environment for IgA induction, and promoted germinal center formation. The cGAMP effect was STING-dependent. Taken together, cGAMP as an HA vaccine adjuvant promoted a STING-dependent NALT environment suitable for the enhancement of IgA production.
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spelling pubmed-57536642018-01-08 cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue Takaki, Hiromi Takashima, Ken Oshiumi, Hiroyuki Ainai, Akira Suzuki, Tadaki Hasegawa, Hideki Matsumoto, Misako Seya, Tsukasa Med Sci (Basel) Article Induction of immunoglobulin (Ig) A in the mucosa of the upper respiratory tract and the nasal cavity protects against influenza virus infection. Cyclic dinucleotides (CDNs) are used as mucosal adjuvants to enhance the immunogenicity of intranasal influenza hemagglutinin (HA) vaccines. The adjuvant activity of 2′3′ cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) on Ig production was investigated in nasal-associated lymphoid tissue (NALT), serum of wild-type C57BL/6J, and stimulator of interferon genes (STING)-deficient mice, which do not recognize cGAMP. Mice were vaccinated intranasally with a HA vaccine with or without the cGAMP adjuvant. IgA and IgG production, T-cell responses, germinal center formation, and cytokine expression in NALT were assayed. cGAMP enhanced IgA and IgG production, and promoted T-cell responses. Intranasal administration of cGAMP activated both NALT and systemic immune cells, induced a favorable cytokine environment for IgA induction, and promoted germinal center formation. The cGAMP effect was STING-dependent. Taken together, cGAMP as an HA vaccine adjuvant promoted a STING-dependent NALT environment suitable for the enhancement of IgA production. MDPI 2017-12-18 /pmc/articles/PMC5753664/ /pubmed/29258267 http://dx.doi.org/10.3390/medsci5040035 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Takaki, Hiromi
Takashima, Ken
Oshiumi, Hiroyuki
Ainai, Akira
Suzuki, Tadaki
Hasegawa, Hideki
Matsumoto, Misako
Seya, Tsukasa
cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue
title cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue
title_full cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue
title_fullStr cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue
title_full_unstemmed cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue
title_short cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue
title_sort cgamp promotes germinal center formation and production of iga in nasal-associated lymphoid tissue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753664/
https://www.ncbi.nlm.nih.gov/pubmed/29258267
http://dx.doi.org/10.3390/medsci5040035
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