Immunoproteasomes are essential for clearance of Listeria monocytogenes in nonlymphoid tissues but not for induction of bacteria-specific CD8+ T cells

J Immunol. 2006 Nov 1;177(9):6238-44. doi: 10.4049/jimmunol.177.9.6238.

Abstract

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 (beta5i(-/-) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Colon / enzymology
  • Colon / immunology
  • Colon / microbiology
  • Epithelial Cells / enzymology
  • Epithelial Cells / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • Hepatocytes / enzymology
  • Hepatocytes / immunology
  • Listeria monocytogenes*
  • Listeriosis / enzymology
  • Listeriosis / immunology*
  • Liver / enzymology*
  • Liver / immunology
  • Liver / microbiology
  • Lymphocyte Activation
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology*
  • Spleen / enzymology
  • Spleen / immunology
  • Spleen / microbiology

Substances

  • Epitopes, T-Lymphocyte
  • Proteasome Endopeptidase Complex