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Critical Roles of NK and CD8⁺ T Cells in Central Nervous System Listeriosis¹

Toshiyuki Hayashi^*,, Shigenori Nagai^*,, Hideki Fujii^*, Yukiko Baba^*,, Eiji Ikeda^2,, Takeshi Kawase and Shigeo Koyasu^3,*

^* Department of Microbiology and Immunology, Department of Neurosurgery, Department of Pathology, Keio University School of Medicine, and Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Tokyo, Japan

Listeria monocytogenes (LM) causes a life-threatening infectious disease affecting the brain of humans and domestic animals. Unfortunately, no adequate murine models for CNS listeriosis exist. Using intraparenchymal injection, we have established a new murine model for CNS listeriosis. Injection of a small volume of bacterial suspension limits the bacteria to the brain parenchyma with no leakage into the ventricular system. This new method enabled us to investigate the progression of and recovery from listerial brain infection, revealing roles for both innate and adaptive immune cells in CNS listeriosis. In the early phase of CNS listeriosis, NK cell-derived IFN- is a critical cytokine in the limitation of bacterial growth by the host defense. During the later phase, CD8⁺ but not CD4⁺ T cells play a critical role and LM-specific CD8⁺ T cells kill LM-infected microglia. Thus, innate and adaptive immune responses combine to successfully eliminate bacteria from the brain.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas (18073015), a Matching Fund Subsidy for Private University, a National Grant-in-Aid for the Establishment of a High-Tech Research Center in a private university, a grant for the Promotion of the Advancement of Education and Research in graduate schools, and a Scientific Frontier Research Grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

² Current address: Department of Pathology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.

³ Address correspondence and reprint requests to Dr. Shigeo Koyasu, Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. E-mail address: koyasu{at}sc.itc.keio.ac.jp

⁴ Abbreviations used in this paper: LM, Listeria monocytogenes; WT, wild type; i.pa., intraparenchymal(ly); i.vt., intraventricular(ly); p.i., postinfection; LLO, listeriolysin O.

This article has been cited by other articles:

				M. Deckert and D. Schluter Comment on "Critical Roles of NK and CD8+ T Cells in Central Nervous System Listeriosis" J. Immunol., November 1, 2009; 183(9): 5437 - 5437. [Full Text] [PDF]

				T. Hayashi, S. Nagai, and S. Koyasu Response to Comment on "Critical Roles of NK and CD8+ T Cells in Central Nervous System Listeriosis" J. Immunol., November 1, 2009; 183(9): 5437 - 5438. [Full Text] [PDF]