The role of mast cells on host defense against lethal herpes simplex virus infection

• Project/Area Number: 24791144
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: University of Yamanashi
• Principal Investigator: AOKI Rui 山梨大学, 医学部附属病院, 助教 (10377541)
• Research Collaborator: KAWAMURA Tatsuyoshi 山梨大学, 医学部附属病院, 講師 (70262657) ; SHIMADA Shinji 山梨大学, 医学工学総合研究部, 教授 (10114505)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: マスト細胞 / 単純ヘルペスウイルス / 自然免疫 / HSV

Research Abstract

Mast cells are known as important players in innate immune responses. The essential contribution of mast cells to bacterial host defense has been well established; however, little is known about their role in viral infections. We have reported that mast cells were critically involved in host defense at herpes simplex virus 2 (HSV-2)-infected sites through TNF-a and IL-6 production. HSV did not directly induce TNF-a or IL-6 production by mast cells, whereas supernatants from HSV-infected keratinocytes induced production of these cytokines by mast cells. Therefore, we examined which factor derived from HSV-infected keratinocytes activated mast cells. We found that IL-33, known as an alarmin in innate immune responses, was elevated in HSV-infected skin and triggered TNF-a and IL-6 production by mast cells.

Research Products

• [Journal Article] Mast cells play a key role in host defense against herpes simplex virus infection through TNF-α and IL-6 production (2013)
  • Author(s): Aoki R, Kawamura T, Goshima F, Ogawa Y, Nakae S, Nakao A, Moriishi K, Nishiyama Y, Shimada S
  • Journal Title: J Invest Dermatol Volume: 133(9) Issue: 9 Pages: 2170-9
  • DOI: 10.1038/jid.2013.150
  • Peer Reviewed
• [Journal Article] Oral administration of the CCR5 inhibitor , maraviroc, blocks HIV ex vivo infection of Langerhans cells within the epithelium (2013)
  • Author(s): Matsuzawa T, Kawamura T, Ogawa Y, Takahashi M, Aoki R, Moriishi K, Koyanagi Y, Gatanaga H, Blauvelt A, Shimada S
  • Journal Title: J Invest Dermatol Volume: 133(12) Issue: 12 Pages: 2803-5
  • DOI: 10.1038/jid.2013.215
  • Peer Reviewed
• [Journal Article] Antimicrobial peptide LL-37 produced by HSV-2-infected keratinocytes enhances HIV infection of Langerhans cells (2013)
  • Author(s): Ogawa Y, Kawamura T, Matsuzawa T, Aoki R, Gee P, Yamashita A, Moriishi K, Yamasaki K, Koyanagi Y. Blauvelt A, Shimada S.
  • Journal Title: Cell Host and Microbe Volume: 13 Issue: 1 Pages: 77-86
  • DOI: 10.1016/j.chom.2012.12.002
  • Peer Reviewed
• [Journal Article] Mast Cells Play a Key Role in Host Defense against Herpes Simplex Virus Infection through TNF-α and IL-6 Production. (2013)
  • Author(s): Aoki R, Kawamura T, Goshima F, Ogawa Y, Nakae S, Nakao A, Moriishi K, Nishiyama Y, Shimada S.
  • Journal Title: J Invest Dermatol. Volume: 133(9) Pages: 2170-2179
  • Peer Reviewed
• [Journal Article] Mast cells play a key role in host defense against herpes simplex virus infection through TNF-α and IL-6 production (2013)
  • Author(s): Rui Aoki
  • Journal Title: Journal of investigative dermatology Volume: 133
  • Peer Reviewed
• [Presentation] The alarmin IL-33 derived from HSV-2-infected keratinocytes triggers mast cell-mediated antiviral innate immunity (2013)
  • Author(s): 青木 類
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh (Scotland)
  • Year and Date: 2013-05-10
• [Presentation] The alarmin IL- 33 derived from HSV- 2- infected keratinocytes triggers mast cell- mediated antiviral innate immunity (2013)
  • Author(s): Rui Aoki
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh International Conference Centre (Edinburgh, Scotland)
• [Presentation] The alarmin IL-33 derived from HSV-2-infected keratinocytes triggers mast cell-mediated antiviral innate immunity (2013)
  • Author(s): Rui Aoki
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh International Conference Centre (Edinburgh, Scotland)
• [Presentation] IL-33 triggers mast cell-mediated innate immunity against lethal herpes simplex virus infection through TNF-α and IL-6 (2012)
  • Author(s): 青木 類
  • Organizer: The 37th Annual Meeting of Japanese Society for Investigative Dermatology
  • Place of Presentation: 沖縄
  • Year and Date: 2012-12-08
• [Presentation] IL-33 triggers mast cell-mediated innate immunity against lethal herpes simplex virus infection through TNF-α and IL-6 (2012)
  • Author(s): 青木 類
  • Organizer: The 42th Annual European Society for Dermatological Research meeting
  • Place of Presentation: Venice(Italy)
  • Year and Date: 2012-09-21
• [Presentation] IL-33 triggers mast cell-mediated innate immunity against lethal herpes simplex virus infection through TNF-α and IL-6 (2012)
  • Author(s): Rui Aoki
  • Organizer: European Society for Dermatological Research
  • Place of Presentation: Plazzo del Casino, Venice Lido Congress Centre (Venice, Italy)
• [Presentation] IL-33 triggers mast cell-mediated innate immunity against lethal herpes simplex virus infection through TNF-α and IL-6 (2012)
  • Author(s): Rui Aoki
  • Organizer: Japanese Society for Investigative Dermatology
  • Place of Presentation: Loisir Hotel & Spa Tower (那覇、沖縄)