Abstract |
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-alpha 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.
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Authors | Takayuki Tsukuba, Shinya Yamamoto, Michiyo Yanagawa, Kuniaki Okamoto, Yoshiko Okamoto, Keiichi I Nakayama, Tomoko Kadowaki, Kenji Yamamoto |
Journal | Journal of biochemistry
(J Biochem)
Vol. 140
Issue 1
Pg. 57-66
(Jul 2006)
ISSN: 0021-924X [Print] England |
PMID | 16877769
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interleukin-6
- Tlr2 protein, mouse
- Tlr4 protein, mouse
- Toll-Like Receptor 2
- Toll-Like Receptor 4
- Tumor Necrosis Factor-alpha
- Cathepsin E
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Topics |
- Animals
- Bacterial Infections
(etiology)
- Cathepsin E
(deficiency)
- Genetic Predisposition to Disease
- Interleukin-6
(biosynthesis)
- Macrophages, Peritoneal
(immunology)
- Male
- Mice
- Mice, Knockout
- Protein Transport
(genetics)
- Staphylococcal Infections
(immunology)
- Toll-Like Receptor 2
(biosynthesis)
- Toll-Like Receptor 4
(biosynthesis)
- Tumor Necrosis Factor-alpha
(biosynthesis)
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