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

Takayuki Tsukuba, Shinya Yamamoto, Michiyo Yanagawa, Kuniaki Okamoto, Yoshiko Okamoto, Keiichi Nakayama, Tomoko Kadowaki, Kenji Yamamoto

Research output: Contribution to journalArticle

39 Citations (Scopus)

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-α 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.

Original languageEnglish
Pages (from-to)57-66
Number of pages10
JournalJournal of biochemistry
Volume140
Issue number1
DOIs
Publication statusPublished - Jul 1 2006

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Cathepsin E
Toll-Like Receptors
Bacterial Infections
Cells
Macrophages
Bacteria
Gram-Positive Bacteria
Gram-Negative Bacteria
Immune System
Aspartic Acid Proteases
Toll-Like Receptor 2
Porphyromonas gingivalis
Immune system
Peritoneal Macrophages
Innate Immunity
Microorganisms
Interleukin-6
Tumor Necrosis Factor-alpha
Defects
Infection

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Cathepsin E-deficient mice show increased susceptibility to bacterial infection associated with the decreased expression of multiple cell surface Toll-like receptors. / Tsukuba, Takayuki; Yamamoto, Shinya; Yanagawa, Michiyo; Okamoto, Kuniaki; Okamoto, Yoshiko; Nakayama, Keiichi; Kadowaki, Tomoko; Yamamoto, Kenji.

In: Journal of biochemistry, Vol. 140, No. 1, 01.07.2006, p. 57-66.

Research output: Contribution to journalArticle

Tsukuba, Takayuki ; Yamamoto, Shinya ; Yanagawa, Michiyo ; Okamoto, Kuniaki ; Okamoto, Yoshiko ; Nakayama, Keiichi ; Kadowaki, Tomoko ; Yamamoto, Kenji. / Cathepsin E-deficient mice show increased susceptibility to bacterial infection associated with the decreased expression of multiple cell surface Toll-like receptors. In: Journal of biochemistry. 2006 ; Vol. 140, No. 1. pp. 57-66.
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