© 2006 The Japanese Biochemical Society.
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Cathepsin E–Deficient Mice Show Increased Susceptibility to Bacterial Infection Associated with the Decreased Expression of Multiple Cell Surface Toll-Like Receptors
1 Departments of Pharmacology, 2 Pediatric Dentistry, and 3 Fixed Prosthodontics, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582; 4 Department of Oral Molecular Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588; 5 Department of Biochemistry, Daiichi University College of Pharmaceutical Sciences, Fukuoka 815-8511; and 6 Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582
To whom correspondence should be addressed. Tel: +81-92-642-6337, Fax: +81-92-642-6342, E-mail: kyama{at}dent.kyushu-u.ac.jp
Cathepsin E, an intracellular aspartic proteinase, is predominantly localized in the endosomal compartments of immune system cells. In the present study, we investigated the role of cathepsin E in immune defense systems against bacterial infection. Cathepsin E–deficient (CatE–/–) mice showed dramatically increased susceptibility to infection with both the Gram-positive bacterium Staphyrococcus aureus, and the Gram-negative bacterium Porphyromonas gingivalis when compared with syngeneic wild-type mice, most likely due to impaired regulation of bacterial elimination. Peritoneal macrophages from CatE–/– mice showed significantly impaired tumor necrosis factor-
and IL-6 production in response to S. aureus and decreased bactericidal activities toward this bacterium. Moreover, the cell surface levels of Toll-like receptor-2 (TLR2) and TLR4, which recognize specific components of Gram-positive and -negative bacteria, respectively, were decreased in CatE–/– macrophages, despite no significant difference in the total cellular expression levels of these receptors between the wild-type and CatE–/– macrophages, implying trafficking defects in these surface receptors in the latter. These results indicate an essential role of cathepsin E in immune defense against invading microorganisms, most probably due to regulation of the cell surface expression of TLR family members required for innate immune responses.
* Both authors contributed wqually to this work.
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