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环状二核苷酸单磷酸腺苷（cGAMP）促进鼻相关淋巴组织生发中心的形成及IgA的产生。

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

作者信息

Takaki Hiromi, Takashima Ken, Oshiumi Hiroyuki, Ainai Akira, Suzuki Tadaki, Hasegawa Hideki, Matsumoto Misako, Seya Tsukasa

机构信息

Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.

Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, South 1, West 17, Chuo-ku, Sapporo 060-8556, Japan.

出版信息

Med Sci (Basel). 2017 Dec 18;5(4):35. doi: 10.3390/medsci5040035.

DOI:10.3390/medsci5040035
PMID:29258267
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5753664/
Abstract

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.

摘要

在上呼吸道和鼻腔黏膜中诱导免疫球蛋白（Ig）A可预防流感病毒感染。环二核苷酸（CDN）用作黏膜佐剂，以增强鼻内流感血凝素（HA）疫苗的免疫原性。在鼻相关淋巴组织（NALT）、野生型C57BL/6J小鼠血清以及不识别2'3'环磷酸鸟苷-腺苷酸（cGAMP）的干扰素基因刺激物（STING）缺陷小鼠中，研究了cGAMP对Ig产生的佐剂活性。给小鼠鼻内接种含或不含cGAMP佐剂的HA疫苗。检测NALT中IgA和IgG的产生、T细胞反应、生发中心形成以及细胞因子表达。cGAMP增强了IgA和IgG的产生，并促进了T细胞反应。鼻内给予cGAMP激活了NALT和全身免疫细胞，诱导了有利于IgA诱导的细胞因子环境，并促进了生发中心形成。cGAMP的作用依赖于STING。综上所述，cGAMP作为HA疫苗佐剂促进了依赖于STING的NALT环境，适合增强IgA的产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/d4c3ddf79f1a/medsci-05-00035-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/a0de1e1d2ab9/medsci-05-00035-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/62f3a0a85951/medsci-05-00035-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/d0fe3c3cb1b0/medsci-05-00035-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/c125911d3651/medsci-05-00035-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/d7a80754240e/medsci-05-00035-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/d4c3ddf79f1a/medsci-05-00035-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/a0de1e1d2ab9/medsci-05-00035-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/62f3a0a85951/medsci-05-00035-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/d0fe3c3cb1b0/medsci-05-00035-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/c125911d3651/medsci-05-00035-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/d7a80754240e/medsci-05-00035-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a59/5753664/d4c3ddf79f1a/medsci-05-00035-g006.jpg

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