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Immunoproteasomes Are Essential for Clearance of Listeria monocytogenes in Nonlymphoid Tissues but Not for Induction of Bacteria-Specific CD8⁺ T Cells¹

Britta Strehl^2,*, Thorsten Joeris^2,, Melanie Rieger^*, Alexander Visekruna, Kathrin Textoris-Taube^*, Stefan H. E. Kaufmann, Peter-Michael Kloetzel^*, Ulrike Kuckelkorn^* and Ulrich Steinhoff^3,

^* Institut für Biochemie, Charité-Universitätsmedizin, Berlin, Germany; and Max-Planck-Institute for Infection Biology, Berlin, Germany

Microbial infections induce the replacement of constitutive proteasomes by immunoproteasomes (I-proteasomes). I-proteasomes support efficient generation of MHC class I epitopes and influence immunodominance hierarchies of CD8⁺ T cells. Recently, the function of I-proteasomes in antimicrobial responses was challenged by showing that the lack of I-proteasomes has no effect on induction and function of lymphocytic choriomeningitis virus-specific CD8⁺ T cells. Here, we show that infection with Listeria monocytogenes rapidly induces I-proteasomes in nonlymphoid tissues, which leads to enhanced generation of protection relevant CD8⁺ T cell epitopes. I-proteasome-deficient mice (5i^–/– mice) exhibited normal frequencies of L. monocytogenes-specific CD8⁺ T cells. However, clearance of L. monocytogenes in liver but not spleen was significantly impaired in I-proteasome-deficient mice. In summary, our studies demonstrate that induction of I-proteasomes is required for CD8⁺ T cell-mediated elimination of L. monocytogenes from nonlymphoid but not lymphoid tissues.

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 Deutsche Forschungsgemeinschaft Project Ku 1261 (to U.K. and U.S.) and the Collaborative Research Center (SFB421).

² B.S. and T.J. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Ulrich Steinhoff, Max-Planck Institute for Infection Biology, Schumannstrasse 21/22, D-10117 Berlin, Germany. E-mail address: steinhoff{at}mpiib-berlin.mpg.de

⁴ Abbreviations used in this paper: I-proteasome, immunoproteasome; LCMV, lymphocytic choriomeningitis virus; wt, wild type; KO, knockout; LLO, listeriolysin O; 2-DE, two-dimensional gel electrophoresis; MS, mass spectrometry; LC-ESI-MS, liquid chromatography-electrospray ionization-ion trap MS; p.i., postinfection.

This article has been cited by other articles:

				B. Strehl, K. Textoris-Taube, S. Jakel, A. Voigt, P. Henklein, U. Steinhoff, P.-M. Kloetzel, and U. Kuckelkorn Antitopes Define Preferential Proteasomal Cleavage Site Usage J. Biol. Chem., June 27, 2008; 283(26): 17891 - 17897. [Abstract] [Full Text] [PDF]