Elucidation of the functional mechanism underlying aspiration pneumonia in lethal influenza and its prevention

• Project/Area Number: 24593149
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Social dentistry
• Research Institution: Osaka University
• Principal Investigator: SEKINE Shinichi 大阪大学, 歯学研究科(研究院), 助教 (70506344)
• Co-Investigator(Kenkyū-buntansha): NAGATA Hideki 大阪大学, 大学院歯学研究科, 准教授 (50260641) ; KUBONIWA Masae 大阪大学, 歯学部附属病院, 講師 (00303983) ; MAEDA Kazuhiko 大阪大学, 大学院歯学研究科, 助教 (00346165)
• Co-Investigator(Renkei-kenkyūsha): ASANUMA Hideki 国立感染研究所, インフルエンザウイルス研究センター, 研究員 (40333570)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 肺炎球菌 / ｒPspA / 舌下免疫 / 樹上細胞 / S. pneumoniae / PspA / 粘膜免疫 / 誤嚥性肺炎 / BALT

Outline of Final Research Achievements

Sublingual (SL) antigen delivery is a non-invasive method-as opposed to invasive ones such as nasal or oral immunization-that avoids possible entry into the olfactory region and the central nervous system, and prevents the need for degradative enzymes that lower the stomach pH. In this study, we showed that SL delivery of pneumococcal surface protein A (PspA) and a cDNA vector expressing RANTES (pCCL5) in mice resulted in increased levels of PspA-specific SIgA antibody (Ab) responses in external secretions, and significantly lowered bacterial density in the lung, nasal washes, and blood. Additionally, SL delivery of pCCL5 cDNA as a mucosal adjuvant significantly increased the number of CCR5+ dendritic cells (DCs) in the periglandular lymph nodes (PGLNs), but not in cervical lymph nodes. These results showed that SL immunization activates CCR5+ SL DCs, which facilitate the induction of PspA-specific SIgA Ab responses and reduce pneumococcal infection.

Research Products

• [Journal Article] Quantitative detection for Porphyromonas gingivalis in tooth pocket and saliva by portable electrochemical DNA sensor linked with PCR. (2015)
  • Author(s): Yamanaka K, Sekine S, Uenoyama T, Wada M, Ikeuchi T, Saito M, Yamaguchi Y, Tamiya E
  • Journal Title: Electroanalysis Volume: in press
  • Peer Reviewed
• [Journal Article] Salivary inflammatory cytokines may be novel markers of carotid atherosclerosis in a Japanese general population: the Suita study. (2014)
  • Author(s): Kosaka T, Kokubo Y, Ono T, Sekine S, Kida M, Kikui M, Yamamoto M, Watanabe M, Amano A, Maeda Y, Miyamoto Y.
  • Journal Title: Atherosclerosis. Volume: 237(1) Issue: 1 Pages: 123-8
  • DOI: 10.1016/j.atherosclerosis.2014.08.046
  • Peer Reviewed
• [Journal Article] Potential roles of CCR5+ CCR6+ Dendritic cells induced by nasalovalbumin plus Flt3 ligand expressing adenovirus for mucosal IgA responses. (2013)
  • Author(s): Fukuyama. Y., et al.
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e60453-e60453
  • DOI: 10.1371/journal.pone.0060453
  • Peer Reviewed
• [Presentation] マイクロチップPCRとキャピラリー電気泳動システムを用いた即時細菌検査システムの開発 (2015)
  • Author(s): 関根伸一、泉井秀介、橋野恵衣、永田英樹、天野敦雄
  • Organizer: 第64回日本口腔衛生学会・総会
  • Place of Presentation: 筑波
  • Year and Date: 2015-05-29
• [Presentation] 唾液メタボローム解析を用いた歯周組織由来の慢性炎症重症度評価モデルの構築 (2015)
  • Author(s): 橋野恵衣、久保庭雅恵、坂中哲人、関根伸一、永田英樹、天野敦雄
  • Organizer: 第64回日本口腔衛生学会・総会
  • Place of Presentation: 筑波
  • Year and Date: 2015-05-29
• [Presentation] Inhibitory effects of curcumin on inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles (2014)
  • Author(s): Shusuke IZUI、Shinichi SEKINE、Hideki NAGATA、Atsuo AMANO
  • Organizer: The 62nd Annual Meeting of Japanese Association for Dental Research
  • Place of Presentation: Osaka（Japan）
  • Year and Date: 2014-12-05
• [Presentation] Inhibitory effect of curcumin on Porphyromonas gingivalis infection (2014)
  • Author(s): Shusuke IZUI、Shinichi SEKINE、Hideki NAGATA、Atsuo AMANO
  • Organizer: The 11th Asian Academy of Preventive Dentidtry
  • Place of Presentation: Beijing（China）
  • Year and Date: 2014-09-14
• [Presentation] Sublingual plasmid cDNA expressing RANTES induces CCR5-positive dendritic cells for the induction of pnumococcal specific SIgA antibody responses. (2013)
  • Author(s): Seine S, Aso K, Fukuyama Y, Fujihashi k, Piao Z, Akeda Y, Oishi T, Briles DE, McGhee JR, Amano A, Fujihashi K
  • Organizer: 16th International Congress of Mucosal Immunology
  • Place of Presentation: Vancouver
• [Presentation] Sublingual Plasmid cDNA Expressing RANTES Induces Protective Immunity To Pneumococcal Infection. (2013)
  • Author(s): Sekine S, Aso K, Ikeda Y, Fujihashi K, Briles DE, McGhee JR, Fujihashi K
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉市
• [Presentation] Novel Sublingual Inductive And Effector Tissues For Antigen-Specific IgA Antibody Responses (2012)
  • Author(s): Shinichi Sekine, Kazuyoshi Aso, Daisuke Tokuhara, Yoshiko Fukuyama, Keiko Fujihashi and Kohtaro Fujihashi
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸