Effect of anti-CD25 monoclonal antibody on chronic otitis media in mice model

• Project/Area Number: 25462648
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Oita University
• Principal Investigator: Hirano Takashi 大分大学, 医学部, 講師 (20305056)
• Co-Investigator(Kenkyū-buntansha): SUZUKI MASASHI 大分大学, 医学部, 教授 (60211314) ; KAWANO TOSHIAKI 大分大学, 医学部, 助教 (30633424)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 慢性中耳炎 / インフルエンザ菌 / 制御性T細胞 / CD25 / CD2５ / 中耳炎

Outline of Final Research Achievements

Nontypeable Haemophilus influenzae (NTHi) is associated with chronic otitis media (COM). In this study, we generated a murine model of COM by using Eustachian tube obstruction and NTHi inoculation into the tympanic bulla, and we investigated the relationship between regulatory T (T reg) cells and chronic inflammation in the middle ear. Middle ear effusions (MEEs) and middle ear mucosae (MEM) were collected at days 3 and 14 and at 1 and 2 months after inoculation. CD4+ CD25+ FoxP3+ T reg cells accumulated in the middle ear, and the percentage of T reg cells in the MEM increased for up to 2 months after inoculation. T reg cell depletion induced a 99.9% reduction of bacteria counts in MEEs and also significantly reduced the ratio of NTHi culture-positive MEE. The levels of these cytokines were also reduced in MEEs. In summary, we developed a murine model of COM and our findings indicate that T reg cells confer infectious tolerance to NTHi in the middle ear.

Research Products

• [Journal Article] Accumulation of regulatory T cells and chronic inflammation in the middle ear in a mouse model of chronic otitis media with effusion induced by combined Eustachian tube blockage and nontypeable Haemophilus influenzae (2015)
  • Author(s): 1. Hirano T, Kodama S, Kawano T, Suzuki M.
  • Journal Title: Infection and Immunity Volume: 84 Issue: 1 Pages: 356-364
  • DOI: 10.1128/iai.01128-15
  • Peer Reviewed / Open Access
• [Presentation] Effect of anti-CD25 monoclonal antibody on chronic otitis media in mice model (2015)
  • Author(s): Takashi Hirano, Satoru Kodama, Munehito Moriyama, Tarou Iwasaki, Yoshinori Kadowaki, Toshiaki Kawano, Masashi Suzuki
  • Organizer: 18th International Symposium on Recent Advances in Otitis Media
  • Place of Presentation: Gayload National Resort and Convention Center, Maryland, USA
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] Analysis of dynamics of Th17 cells in chronic middle ear inflammation induced by nontypeable Haemophilus influenzae (2013)
  • Author(s): Takashi Hirano, Satoru Kodama, Toshiaki Kawano, Munehito Moriyama, Masashi Suzuki
  • Organizer: 7th Extraordinary International Symposium on Recent Advances in Otitis Media
  • Place of Presentation: Clarion Hotel Sign, Stockholm, Sweden
• [Presentation] Neutrophils with triggering receptor expressed on myeloid cells (TREM)-1 expression enhance bacterial clearance from the nose in C3H/HeN mice more than in C3H/HeJ mice. (2013)
  • Author(s): Takashi Hirano, Munehito Moriyama, Toshiaki Kawano, Yoshinori Kadowaki, Taro Iwasaki, Satoru Kodama, Masashi Suzuki
  • Organizer: 7th International Symposium on Recent Advances in rhino sinusitis and nasal polyposis
  • Place of Presentation: Kunibiki Messe, Simane, Japan
• [Presentation] Innate immunity responses to common respiratory pathogens in the upper airways (2013)
  • Author(s): akashi Hirano1, Masashi Suzuki
  • Organizer: 18th Congress of the APSR
  • Place of Presentation: Pacifico Yokohama, Yokohama, Japan
  • Invited