The host adherens junction molecule nectin-1 is downregulated in Chlamydia trachomatis-infected genital epithelial cells.
Nectin-1, a member of the immunoglobulin superfamily, is a Ca(2+)-independent cell adhesion protein implicated in the organization of E-cadherin-based adherens junctions (AJs) and claudin-based tight junctions (TJs) in epithelial cells. Nectin-1 also regulates cell-cell adhesion and cell polarization in a Cdc42- and Rac-dependent manner. Western blot analyses demonstrated that accumulation of host nectin-1 is decreased by 85 % at 48 hours post-infection (h.p.i.) in Chlamydia trachomatis serovar E-infected HeLa cells. Time-course experiments demonstrated that this decrease was sustained to 60 h.p.i. Nectin-1 downregulation in C. trachomatis-infected cells was prevented by both chloramphenicol exposure and prior inactivation of the chlamydiae with UV light, demonstrating that active C. trachomatis replication was required. Penicillin G-exposure studies demonstrated that nectin-1 accumulation was also altered during persistent infection. Finally, RT-PCR analyses indicated that chlamydial infection did not alter accumulation of any nectin-1 transcripts, demonstrating that nectin-1 accumulation is reduced at a post-transcriptional level. Intesrestingly, N-cadherin-dependent cell-cell junctions can be disrupted by C. trachomatis infection, as reported by Prozialeck et al. (2002). Because interaction of nectin molecules on adjacent cells is essential for AJ formation, these data suggest that C. trachomatis may disrupt AJs, at least in part, by diminishing nectin-1 accumulation. Notably, release of chlamydiae-infected epithelial cells has been observed both in vitro from polarized monolayers and in vivo from tissues, suggesting that chlamydia-modulated downregulation of adhesion molecules and the subsequent disruption of host cell adherence may be involved in chlamydial dissemination or pathogenesis.
Sun
Jingru
J
Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Kintner
Jennifer
J
Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Schoborg
Robert V
RV
Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
D022005:Adherens Junctions / Q000382:microbiology / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002692:Chlamydia trachomatis / Q000502:physiology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000382:microbiology*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D000075983:Nectins; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D012333:RNA, Messenger