Type 1-polarized dendritic cells pulsed with ESAT-6 are a potent immunogen against tuberculosis

• Project/Area Number: 24591160
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: YUTARO Nakamura 浜松医科大学, 医学部附属病院, 講師 (60436962)
• Co-Investigator(Kenkyū-buntansha): SUDA Takafumi 浜松医科大学, 医学部, 教授 (30291397) ; NAGATA Toshi 浜松医科大学, 医学部, 教授 (90275024)
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 結核 / 樹状細胞 / 細胞性免疫 / ワクチン / 結核症

Outline of Final Research Achievements

The development of effective vaccine strategies for tuberculosis(TB) is one of the major frontiers of medical research. Our previous studies showed that type-1 polarized dendritic cell (alphaDC1) vaccine is a promising approach for eliciting protective immunity against intracellular bacteria in animal model. Here we showed that alpha DC1 from TB patients could significantly induce antigen specific type-1 immunity. Monocyte-derived DCs from TB patients were induced to mature using a "standard" cytokine cocktail or using an alpha-type 1-polarized DC (alphaDC1) cocktail and were pulsed with established TB antigen (ESAT-6). AlphaDC1 secreted substantially higher levels of IL-12p70 than standard DCs. Furthermore alphaDC1 induced much higher numbers of interferon gamma producing functional T cells against TB. The current demonstration that TB antigen pulsed alphaDC1 are potent inducers of TB-specific T cells helps to develop improved immunotherapies.

Research Products

• [Journal Article] Prognostic Significance of Anti-Aminoacyl-tRNA Synthetase Antibodies in Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease: A Retrospective Case Control Study. (2015)
  • Author(s): Hozumi H, Enomoto N, Kono M, Fujisawa T, Inui N, Nakamura Y, Sumikawa H, Johkoh T, Nakashima R, Imura Y, Mimori T, Suda T
  • Journal Title: PLoS One Volume: 19;10(3) Issue: 3 Pages: e0120313-e0120313
  • DOI: 10.1371/journal.pone.0120313
  • Peer Reviewed / Open Access
• [Journal Article] Usual interstitial pneumonia preceding collagen vascular disease: a retrospective case control study of patients initially diagnosed with idiopathic pulmonary fibrosis. (2014)
  • Author(s): Kono M, Nakamura Y, Enomoto N, Hashimoto D, Fujisawa T, Inui N, Maekawa M, Suda T, Colby TV, Chida K
  • Journal Title: PLOS ONE Volume: 9 Issue: 4 Pages: e94775-e94775
  • DOI: 10.1371/journal.pone.0094775
  • Peer Reviewed / Open Access
• [Journal Article] Plasma connective tissue growth factor levels as potential biomarkers of airway obstruction in patients with asthma. Ann Allergy Asthma Immunol. (2014)
  • Author(s): Kato M, Fujisawa T, Hashimoto D, Kono M, Enomoto N, Nakamura Y, Inui N, Hamada E, Miyazaki O, Kurashita S, Maekawa M, Suda T
  • Journal Title: Ann Allergy Asthma Immunol. Volume: 113 (3) Issue: 3 Pages: 295-300
  • DOI: 10.1016/j.anai.2014.05.026
  • Peer Reviewed / Open Access
• [Journal Article] TLR-Mediated Airway IL-17C Enhances Epithelial Host Defense in an Autocrine/Paracrine Manner. (2014)
  • Author(s): Kusagaya H, Fujisawa T*, Yamanaka K, Mori K, Hashimoto D, Enomoto N, Inui N, Nakamura Y, Wu R, Maekawa M, Suda T, Chida K.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: 50 Issue: 1 Pages: 30-39
  • DOI: 10.1165/rcmb.2013-0130oc
  • Peer Reviewed
• [Journal Article] Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study. (2013)
  • Author(s): Hozumi H, Nakamura Y, Johkoh T, Sumikawa H, Colby TV, Kono M, Hashimoto D, Enomoto N, Fujisawa T, Inui N, Suda T, Chida K.
  • Journal Title: BMJ Open. Volume: 3 Issue: 9 Pages: e003132-e003132
  • DOI: 10.1136/bmjopen-2013-003132
  • Peer Reviewed
• [Journal Article] Amount of elastic fibers predicts prognosis of idiopathic pulmonary fibrosis. (2013)
  • Author(s): Enomoto N, Suda T, Kono M, Kaida Y, Hashimoto D, Fujisawa T, Inui N, Nakamura Y, Imokawa S, Funai K, Chida K.
  • Journal Title: Respir Med. Volume: 107 Issue: 10 Pages: 1608-1616
  • DOI: 10.1016/j.rmed.2013.08.008
  • Peer Reviewed
• [Journal Article] Pharmacokinetic analysis of doripenem in elderly patients with nosocomial pneumonia (2013)
  • Author(s): Harada M, Inui N, Suda T, Nakamura Y, Wajima T, Matsuo Y, Chida K.
  • Journal Title: Int J Antimicrob Agents Volume: 42(2) Issue: 2 Pages: 149-54
  • DOI: 10.1016/j.ijantimicag.2013.03.012
  • Peer Reviewed
• [Journal Article] Multidetector-row computed tomography assessment of adding budesonide/formoterol to tiotropium in patients with chronic obstructive pulmonary disease. (2013)
  • Author(s): Yasui H, Inui N, Furuhashi K, Nakamura Y, Uto T, Sato J, Yasuda K, Takehara Y, Suda T, Chida K.
  • Journal Title: Pulm Pharmacol Ther. Volume: 26 Issue: 3 Pages: 336-41
  • DOI: 10.1016/j.pupt.2013.01.005
  • Peer Reviewed
• [Journal Article] Alveolar nitric oxide concentration reflects peripheral airway obstruction in stable asthma. (2013)
  • Author(s): Fujisawa T, Yasui H, Akamatsu T, Hashimoto D, Enomoto N, Inui N, Nakamura Y, Maekawa M, Suda T, Chida K.
  • Journal Title: Respirology Volume: 18 Issue: 3 Pages: 522-7
  • DOI: 10.1111/resp.12031
  • Peer Reviewed
• [Journal Article] Idiopathic pleuroparenchymal fibroelastosis: consideration of a clinicopathological entity in a series of Japanese patients. (2012)
  • Author(s): Kusagaya H, Nakamura Y, Kono M, Kaida Y, Kuroishi S, Enomoto N, Fujisawa T, Koshimizu N, Yokomura K, Inui N, Suda T, Colby TV, Chida K
  • Journal Title: BMC Pulm Med Volume: 72 Issue: 1 Pages: 1-7
  • DOI: 10.1186/1471-2466-12-72
  • Peer Reviewed
• [Journal Article] Expression and function of multidrug resistance protein 1 and multidrug resistance-associated protein 1 in lung dendritic cells from aging mice. (2012)
  • Author(s): Inui N, Hasegawa H, Suda T, Nakamura Y, Watanabe H, Chida K.
  • Journal Title: J Gerontol A Biol Sci Med Sci. Volume: 67 Issue: 10 Pages: 1049-55
  • DOI: 10.1093/gerona/gls069
  • Peer Reviewed
• [Journal Article] Mouse CD11bhigh lung dendritic cells have more potent capability to induce IgA than CD103+ lung dendritic cells in vitro． (2012)
  • Author(s): Suzuki Y
  • Journal Title: Am J Respir Cell Mol Biol Volume: 46(6) Issue: 6 Pages: 773-780
  • DOI: 10.1165/rcmb.2011-0329oc
  • Peer Reviewed
• [Presentation] Idiopathic pleuroparenchymal fibroelastosis: Possibility of making a diagnosis without surgical lung biopsy (2014)
  • Author(s): Yutaro Nakamura, Yasuomi Satake, Hideki Kusagaya, Yoshiyuki Oyama, Masato Kono, Noriyuki Enomoto, Tomoyuki Fujisawa, Naoki Inui, Thomas V Colby, Takafumi Suda
  • Organizer: 18th International Colloquium on Lung and Airway Fibrosis
  • Place of Presentation: Mont Trenbrant, Canada
  • Year and Date: 2014-09-20 – 2014-09-24
• [Presentation] Biopy-Proven Rheumatoid Lung Disease : Relationship between Histopathologic Features and Mortality (2013)
  • Author(s): Nakamura Y, Suda T, Kono M, Hozumi H, Hashimoto D, Enomoto N, Fujisawa T, Inui N, Imokawa S, Yasuda K, Shirai T, Colby TV, Chida K
  • Organizer: 109 th American Thoracic Society International Conference
  • Place of Presentation: Philadelphia
• [Presentation] Enhancement of protective immunity against intracellular bacteria using type-1 polarized dendritic cell (DC) vaccine. (2013)
  • Author(s): Nakamura Y, Kono M, Suda T, Uchijima M, Tsujimura K, Nagata T, Giermasz AS, Kalinski P, Nakamura H, Chida K.
  • Organizer: Keystone symposia
  • Place of Presentation: Keystone, CO, USA
• [Book] インフォームドコンセ ントのための図説シリーズ びまん性肺疾患と特発性間質性肺炎 (2014)
  • Author(s): 中村祐太郎, 須田隆文
  • Total Pages: 5
  • Publisher: 医薬ジャーナル社