Cathepsin E-deficient mice show increased susceptibility to bacterial infection associated with the decreased expression of multiple cell surface Toll-like receptors.

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.

• 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)

Chemical References

• Interleukin-6
• Tlr2 protein, mouse
• Tlr4 protein, mouse
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Cathepsin E

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)