title: CD1d degradation in Chlamydia trachomatis-infected epithelial cells is the result of both cellular and chlamydial proteasomal activity.
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.
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Quayle
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ficarra
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Ibana
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawana
authors.forename: Huixia
authors.initials: H
authors.lastname: Yang
authors.forename: Luis
authors.initials: L
authors.lastname: Marrero
authors.forename: Sujata
authors.initials: S
authors.lastname: Yavagal
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Greene
authors.forename: You-Xun
authors.initials: YX
authors.lastname: Zhang
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pyles
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Schust
mesh_terms: D000595:Amino Acid Sequence; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000201:enzymology* / Q000276:immunology / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D047468:Immunoprecipitation; D008297:Male; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D046988:Proteasome Endopeptidase Complex