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

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

doi:10.3390/medsci5040035

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

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

Authors

Hiromi Takaki^{1

2}, Ken Takashima³, Hiroyuki Oshiumi^{4

5}, Akira Ainai⁶, Tadaki Suzuki⁷, Hideki Hasegawa⁸, Misako Matsumoto⁹, Tsukasa Seya¹⁰

Affiliations

¹ Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan. tahiromi@med.hokudai.ac.jp.
² 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. tahiromi@med.hokudai.ac.jp.
³ Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan. ktakashima@med.hokudai.ac.jp.
⁴ Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan. oshiumi@kumamoto-u.ac.jp.
⁵ Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjyo, Chuou-ku, Kumamoto 860-0811, Japan. oshiumi@kumamoto-u.ac.jp.
⁶ Department of Pathology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan. ainai@nih.go.jp.
⁷ Department of Pathology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan. tksuzuki@niid.go.jp.
⁸ Department of Pathology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan. hasegawa@nih.go.jp.
⁹ Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan. matumoto@pop.med.hokudai.ac.jp.
¹⁰ Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan. seya-tu@pop.med.hokudai.ac.jp.

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.

Keywords: IgA; NALT; STING; cGAMP.