CD1d degradation in Chlamydia trachomatis-infected epithelial cells is the result of both cellular and chlamydial proteasomal activity

Kei Kawana, Alison J. Quayle, Mercedes Ficarra, Joyce A. Ibana, Li Shen, Yukiko Kawana, Huixia Yang, Luis Marrero, Sujata Yavagal, Sheila J. Greene, You Xun Zhang, Richard Pyles, Richard S. Blumberg, Danny J. Schust

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Chlamydia trachomatis is an obligate intracellular pathogen that can persist in the urogenital tract. Mechanisms by which C. trachomatis evades clearance by host innate immune responses are poorly described. CD1d is MHC-like, is expressed by epithelial cells, and can signal innate immune responses by NK and NKT cells. Here we demonstrate that C. trachomatis infection down-regulates surface-expressed CD1d in human penile urethral epithelial cells through proteasomal degradation. A chlamydial proteasome-like activity factor (CPAF) interacts with the CD1d heavy chain, and CPAF-associated CD1d heavy chain is then ubiquitinated and directed along two distinct proteolytic pathways. The degradation of immature glycosylated CD1d was blocked by the proteasome inhibitor lactacystin but not by MG132, indicating that degradation was not via the conventional proteasome. In contrast, the degradation of non-glycosylated CD1d was blocked by lactacystin and MG132, consistent with conventional cellular cytosolic degradation of N-linked glycoproteins. Immunofluorescent microscopy confirmed the interruption of CD1d trafficking to the cell surface, and the dislocation of CD1d heavy chains into both the cellular cytosol and the chlamydial inclusion along with cytosolic CPAF. C. trachomatis targeted CD1d toward two distinct proteolytic pathways. Decreased CD1d surface expression may help C. trachomatis evade detection by innate immune cells and may promote C. trachomatis persistence.

Original languageEnglish (US)
Pages (from-to)7368-7375
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number10
DOIs
StatePublished - Mar 2 2007

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Chlamydia trachomatis
Proteasome Endopeptidase Complex
Epithelial Cells
Degradation
Innate Immunity
Proteasome Inhibitors
Pathogens
Chlamydia Infections
Natural Killer T-Cells
Glycoproteins
Microscopic examination
Natural Killer Cells
Cytosol
Microscopy
Down-Regulation
lactacystin
benzyloxycarbonylleucyl-leucyl-leucine aldehyde

ASJC Scopus subject areas

  • Biochemistry

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CD1d degradation in Chlamydia trachomatis-infected epithelial cells is the result of both cellular and chlamydial proteasomal activity. / Kawana, Kei; Quayle, Alison J.; Ficarra, Mercedes; Ibana, Joyce A.; Shen, Li; Kawana, Yukiko; Yang, Huixia; Marrero, Luis; Yavagal, Sujata; Greene, Sheila J.; Zhang, You Xun; Pyles, Richard; Blumberg, Richard S.; Schust, Danny J.

In: Journal of Biological Chemistry, Vol. 282, No. 10, 02.03.2007, p. 7368-7375.

Research output: Contribution to journalArticle

Kawana, K, Quayle, AJ, Ficarra, M, Ibana, JA, Shen, L, Kawana, Y, Yang, H, Marrero, L, Yavagal, S, Greene, SJ, Zhang, YX, Pyles, R, Blumberg, RS & Schust, DJ 2007, 'CD1d degradation in Chlamydia trachomatis-infected epithelial cells is the result of both cellular and chlamydial proteasomal activity', Journal of Biological Chemistry, vol. 282, no. 10, pp. 7368-7375. https://doi.org/10.1074/jbc.M610754200
Kawana, Kei ; Quayle, Alison J. ; Ficarra, Mercedes ; Ibana, Joyce A. ; Shen, Li ; Kawana, Yukiko ; Yang, Huixia ; Marrero, Luis ; Yavagal, Sujata ; Greene, Sheila J. ; Zhang, You Xun ; Pyles, Richard ; Blumberg, Richard S. ; Schust, Danny J. / CD1d degradation in Chlamydia trachomatis-infected epithelial cells is the result of both cellular and chlamydial proteasomal activity. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 10. pp. 7368-7375.
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AU - Kawana, Kei

AU - Quayle, Alison J.

AU - Ficarra, Mercedes

AU - Ibana, Joyce A.

AU - Shen, Li

AU - Kawana, Yukiko

AU - Yang, Huixia

AU - Marrero, Luis

AU - Yavagal, Sujata

AU - Greene, Sheila J.

AU - Zhang, You Xun

AU - Pyles, Richard

AU - Blumberg, Richard S.

AU - Schust, Danny J.

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N2 - Chlamydia trachomatis is an obligate intracellular pathogen that can persist in the urogenital tract. Mechanisms by which C. trachomatis evades clearance by host innate immune responses are poorly described. CD1d is MHC-like, is expressed by epithelial cells, and can signal innate immune responses by NK and NKT cells. Here we demonstrate that C. trachomatis infection down-regulates surface-expressed CD1d in human penile urethral epithelial cells through proteasomal degradation. A chlamydial proteasome-like activity factor (CPAF) interacts with the CD1d heavy chain, and CPAF-associated CD1d heavy chain is then ubiquitinated and directed along two distinct proteolytic pathways. The degradation of immature glycosylated CD1d was blocked by the proteasome inhibitor lactacystin but not by MG132, indicating that degradation was not via the conventional proteasome. In contrast, the degradation of non-glycosylated CD1d was blocked by lactacystin and MG132, consistent with conventional cellular cytosolic degradation of N-linked glycoproteins. Immunofluorescent microscopy confirmed the interruption of CD1d trafficking to the cell surface, and the dislocation of CD1d heavy chains into both the cellular cytosol and the chlamydial inclusion along with cytosolic CPAF. C. trachomatis targeted CD1d toward two distinct proteolytic pathways. Decreased CD1d surface expression may help C. trachomatis evade detection by innate immune cells and may promote C. trachomatis persistence.

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