PMID- 30036800 OWN - NLM STAT- MEDLINE DCOM- 20190327 LR - 20190327 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 101 DP - 2018 Sep TI - Th17 activation by dendritic cells stimulated with gamma-irradiated Streptococcus pneumoniae. PG - 344-352 LID - S0161-5890(18)30576-5 [pii] LID - 10.1016/j.molimm.2018.07.023 [doi] AB - Dendritic cells (DCs) play an important role in antigen presentation, which is an essential step for the induction of antigen-specific adaptive immunity. Inactivated bacterial whole cell vaccines have been widely used to prevent many bacterial infections because they elicit good immunogenicity due to the presence of various antigens and are relatively inexpensive and easy to manufacture. Recently, gamma-irradiated whole cells of nonencapsulated Streptococcus pneumoniae were developed as a broad-spectrum and serotype-independent multivalent vaccine. In the present study, we generated gamma-irradiated S. pneumoniae (r-SP) and investigated its capacity to stimulate mouse bone marrow-derived DCs (BM-DCs) in comparison with heat-inactivated and formalin-inactivated S. pneumoniae (h-SP and f-SP, respectively). r-SP showed an attenuated binding and internalization level to BM-DCs when compared to h-SP or f-SP. r-SP weakly induced the expression of CD80, CD83, CD86, MHC class I, and PD-L2 compared with h-SP or f-SP. Furthermore, r-SP less potently induced IL-6, TNF-alpha, and IL-23 expression than h-SP or f-SP but more potently induced IL-1beta expression than h-SP or f-SP in BM-DCs. Since Th17-mediated immune responses are known to be important for the protection against pneumococcal infections, r-SP-primed DCs were co-cultured with splenocytes or splenic CD4(+) T cells. Interestingly, r-SP-sensitized BM-DCs markedly induced IL-17A(+) CD4(+) T cells whereas h-SP- or f-SP-sensitized BM-DCs weakly induced them. Collectively, these results suggest that r-SP could be an effective pneumococcal vaccine candidate eliciting Th17-mediated immune responses by stimulation of DCs. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Kim, Hyun Young AU - Kim HY AD - Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea. FAU - Kim, Sun Kyung AU - Kim SK AD - Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea. FAU - Seo, Ho Seong AU - Seo HS AD - Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea. FAU - Jeong, Soyoung AU - Jeong S AD - Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea. FAU - Ahn, Ki Bum AU - Ahn KB AD - Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea; Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea. FAU - Yun, Cheol-Heui AU - Yun CH AD - Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea. FAU - Han, Seung Hyun AU - Han SH AD - Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: shhan-mi@snu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180721 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (B7-H1 Antigen) RN - 0 (Biomarkers) RN - 0 (Cd274 protein, mouse) RN - 0 (Cytokines) RN - 0 (Pdcd1lg2 protein, mouse) RN - 0 (Programmed Cell Death 1 Ligand 2 Protein) RN - 0 (Receptors, Antigen, T-Cell, gamma-delta) RN - 1HG84L3525 (Formaldehyde) SB - IM MH - Animals MH - B7-H1 Antigen/metabolism MH - Bacterial Adhesion/radiation effects MH - Biomarkers/metabolism MH - Bone Marrow Cells/immunology MH - Cell Differentiation MH - Cytokines/metabolism MH - Dendritic Cells/*immunology/*microbiology MH - Endocytosis MH - Formaldehyde MH - *Gamma Rays MH - Hot Temperature MH - Lymphocyte Activation/*immunology MH - Mice MH - Programmed Cell Death 1 Ligand 2 Protein/metabolism MH - Receptors, Antigen, T-Cell, gamma-delta/metabolism MH - Spleen/metabolism MH - Streptococcus pneumoniae/*immunology/*radiation effects MH - Th17 Cells/*immunology OTO - NOTNLM OT - Dendritic cell OT - Gamma-Irradiation OT - Streptococcus pneumoniae OT - Th17 OT - Vaccine EDAT- 2018/07/24 06:00 MHDA- 2019/03/28 06:00 CRDT- 2018/07/24 06:00 PHST- 2018/04/04 00:00 [received] PHST- 2018/06/22 00:00 [revised] PHST- 2018/07/15 00:00 [accepted] PHST- 2018/07/24 06:00 [pubmed] PHST- 2019/03/28 06:00 [medline] PHST- 2018/07/24 06:00 [entrez] AID - S0161-5890(18)30576-5 [pii] AID - 10.1016/j.molimm.2018.07.023 [doi] PST - ppublish SO - Mol Immunol. 2018 Sep;101:344-352. doi: 10.1016/j.molimm.2018.07.023. Epub 2018 Jul 21.