Immunoproteasomes are essential for clearance of Listeria monocytogenes in nonlymphoid tissues but not for induction of bacteria-specific CD8+ T cells.
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.
Strehl
Britta
B
Institut für Biochemie, Charité-Universitätsmedizin, Berlin, Germany.
Joeris
Thorsten
T
Rieger
Melanie
M
Visekruna
Alexander
A
Textoris-Taube
Kathrin
K
Kaufmann
Stefan H E
SH
Kloetzel
Peter-Michael
PM
Kuckelkorn
Ulrike
U
Steinhoff
Ulrich
U
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003106:Colon / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D022781:Hepatocytes / Q000201:enzymology / Q000276:immunology; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000201:enzymology / Q000276:immunology*; D008099:Liver / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000201:enzymology / Q000276:immunology / Q000382:microbiology
D018984:Epitopes, T-Lymphocyte; D046988:Proteasome Endopeptidase Complex