Role of PD-1 in Mycobacterium tuberculosis infection

2012 Fiscal Year Final Research Report

• Project/Area Number: 23890087
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kyoto University
• Principal Investigator: SAKAI Shunsuke 京都大学, 大学院・医学研究科, 研究員 (50609063)
• Project Period (FY): 2011 – 2012
• Keywords: 細菌学 / 感染症 / 免疫学

Research Abstract

CD4 T cell-mediated immune response is essential for the control of M. tuberculosis (Mtb) infection. Recent studies of the programmed cell death 1 (PD-1) receptor have provided novel insights into the inhibition of T-cell activation in infectious diseases. To clarify the role of PD-1 in Mtb infection, I investigated the course of Mtb infection in PD-1 KO mice. After infection, PD-1 KO mice die rapidly owing to severe lung damage. PD-1 KO mice developed higher numbers of IFN-γ-producing CD4 T cells compared to control mice. By using adoptive transfer and antibody blockade experiments, PD-1 deficiency in CD4 T cells and IFN-γ production by CD4 T cells aresufficient to cause the increased susceptibility to infection. These data show that PD-1 is essential in limiting CD4 T cell-mediated pathology in Mtb infection.

Research Products

• [Journal Article] Two genetically -related multidrug-resistant Mycobacterium tuberculosis strains induce divergent outcomes of infection in two human macrophage models (2013)
  • Author(s): Yokobori, N., Lopez, B., Geffner, L., Sabio y Garcia, C., Schierloh, P., Barrera, L., Barrera, S., Sakai, S., Kawamura, I., Mitsuyama, M., Ritacco, V. and del Carmen Sasiain,M.
  • Journal Title: Infection, Genetics and Evolution Volume: 16 Pages: 151-156
  • DOI: DOI:10.1016/j.meegid.2013.01.007
  • Peer Reviewed
• [Journal Article] Cutting Edge: Nitric oxide inhibits the NLRP3 inflammasome (2012)
  • Author(s): Hernandez-Cuellar, E., Tsuchiya, K., Hara, H., Fang, R., Sakai, S., Kawamura, I., Akira, S. and Mitsuyama, M
  • Journal Title: Journal of Immunology Volume: 189 Pages: 5113-5117
  • DOI: DOI:10.4049/jimmunol.1202479
  • Peer Reviewed
• [Journal Article] Critical role of ASC inflammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniaeinfection (2011)
  • Author(s): Fang, R., Tsuchiya, K., Kawamura, I., Shen, Y., Hara, H., Sakai, S., Yamamoto, T., Fernandes Alnemri, T., Yang, R., Hernandez-Cuellar, E., Dewamitta, S. R., Xu, Y., Qu, H., Alnemri, E. S. and Mitsuyama, M
  • Journal Title: Journal of Immunology Volume: 187 Pages: 4890-4899
  • DOI: DOI:10.4049/jimmunol.1100381
  • Peer Reviewed
• [Journal Article] Expression of the Mycobacterium tuberculosisPPE37 protein in M. smegmatis induces low TNF-α and IL-6 production in murine macrophages (2011)
  • Author(s): Daim, S., Kawamura, I., Tsuchiya, K., Hara, H., Kurenuma, T., Shen, Y., Dewamitta, S. R., Sakai, S., Qu, H., Nomura, T. and Mitsuyama, M
  • Journal Title: Journal of Medical Microbiology Volume: 60 Pages: 582-591
  • DOI: DOI:10.1099/jmm.0.026047-0
  • Peer Reviewed
• [Presentation] PD-1 deficiency causes CD4 T cell-mediated exacerbation of Mycobacterium tuberculosis infection (2012)
  • Author(s): Sakai, S., Kawamura, I., Tsuchiya, K. and Mitsuyama, M
  • Organizer: 第85回日本細菌学会総会
  • Place of Presentation: 長崎ブリックホール
  • Year and Date: 2012-03-28
• [Presentation] 結核菌感染において免疫抑制受容体PD-1は、Th1型免疫応答を制御し宿主に対して防御的にはたらく (2011)
  • Author(s): 酒井 俊祐、河村 伊久雄、土屋 晃介、光山 正雄
  • Organizer: 第64回日本細菌学会関西支部総会
  • Place of Presentation: 大阪府立大学
  • Year and Date: 2011-11-19
• [Presentation] PD-1 regulates the balance between protective and pathologic immune responses during murine tuberculosis (2011)
  • Author(s): Sakai, S., Kawamura, I., Tsuchiya, K. Okazaki, T. and Mitsuyama, M
  • Organizer: The 13th International Congress of Bacteriology and Applied Microbiology
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2011-09-08
• [Book] 基礎各論 結核菌感染の病態 (2012)
  • Author(s): 酒井 俊祐, 光山 正雄
  • Publisher: 臨床と微生物
• [Remarks] 京都大学大学院 医学研究科 微生物感染症学
  • URL: http://www.med.kyoto-u.ac.jp/J/grad_school/introduction/1204/