Nectin-1, a member of the immunoglobulin superfamily, is a Ca2+-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.
ArnoJ. N.,
RickerV. A.,
BatteigerB. E.,
KatzB. P.,
CaineV. A.,
JonesR. B.1990; Interferon-gamma in endocervical secretions of women infected with Chlamydia trachomatis . J Infect Dis 162:1385–1389
BragaV. M.,
MacheskyL. M.,
HallA.,
HotchinN. A.1997; The small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell–cell contacts. J Cell Biol 137:1421–1431
BragaV. M.,
Del MaschioA.,
MacheskyL.,
DejanaE.1999; Regulation of cadherin function by Rho and Rac: modulation by junction maturation and cellular context. Mol Biol Cell 10:9–22
DarvilleT.2000; Chlamydia spp. In Persistent Bacterial Infections pp 229–261 Edited by
NataroJ. P.,
BlazerM. J.,
Cunningham-RundlesS.
Washington, DC: American Society for Microbiology;
DekaS.,
VanoverJ.,
SunJ.,
KintnerJ.,
WhittimoreJ.,
SchoborgR. V.2007; An early event in the herpes simplex virus type-2 replication cycle is sufficient to induce Chlamydia trachomatis persistence. Cell Microbiol 9:725–737
FanT.,
LuH.,
HuH.,
ShiL.,
McClartyG. A.,
NanceD. M.,
GreenbergA. H.,
ZhongG.1998; Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation. J Exp Med 187:487–496
HackstadtT.1999; Cell biology. In Chlamydia: Intracellular Biology, Pathogenesis, and Immunity pp 101–138 Edited by
StephensR. S.
Washington, DC: American Society for Microbiology;
HatchT.1999; Developmental biology. In Chlamydia: Intracellular Biology, Pathogenesis, and Immunity pp 29–67 Edited by
StephensR. S.
Washington, DC: American Society for Microbiology;
HeuerD.,
BrinkmannV.,
MeyerT. F.,
SzczepekA. J.2003; Expression and translocation of chlamydial protease during acute and persistent infection of the epithelial HEp-2 cells with Chlamydophila ( Chlamydia ) pneumoniae . Cell Microbiol 5:315–322
HondaT.,
ShimizuK.,
KawakatsuT.,
FukuharaA.,
IrieK.,
NakamuraT.,
MatsudaM.,
TakaiY.2003; Cdc42 and Rac small G proteins activated by trans -interactions of nectins are involved in activation of c -Jun N-terminal kinase, but not in association of nectins and cadherin to form adherens junctions, in fibroblasts. Genes Cells 8:481–491
JepsonM. A.,
Collares-BuzatoC. B.,
ClarkM. A.,
HirstB. H.,
SimmonsN. L.1995; Rapid disruption of epithelial barrier function by Salmonella typhimurium is associated with structural modification of intercellular junctions. Infect Immun 63:356–359
KaneC. D.,
ByrneG. I.1998; Differential effects of gamma interferon on Chlamydia trachomatis growth in polarized and nonpolarized human epithelial cells in culture. Infect Immun 66:2349–2351
KawakatsuT.,
ShimizuK.,
HondaT.,
FukuharaT.,
HoshinoT.,
TakaiY.2002; Trans -interactions of nectins induce formation of filopodia and lamellipodia through the respective activation of Cdc42 and Rac small G proteins. J Biol Chem 277:50749–50755
MajeedM.,
GustafssonM.,
KihlstromE.,
StendahlO.1993; Roles of Ca2+ and F-actin in intracellular aggregation of Chlamydia trachomatis in eucaryotic cells. Infect Immun 61:1406–1414
NelsonD. E.,
VirokD. P.,
WoodH.,
RoshickC.,
JohnsonR. M.,
WhitmireW. M.,
CraneD. D.,
Steele-MortimerO.,
KariL.other authors2005; Chlamydial IFN- γ immune evasion is linked to host infection tropism. Proc Natl Acad Sci U S A 102:10658–10663
SearsC. L.2000; Molecular physiology and pathophysiology of tight junctions V. Assault of the tight junction by enteric pathogens. Am J Physiol Gastrointest Liver Physiol 279:G1129–G1134
SoloffB. L.,
RankR. G.,
BarronA. L.1985; Electron microscopic observations concerning the in vivo uptake and release of the agent of guinea-pig inclusion conjunctivitis ( Chlamydia psittaci ) in guinea-pig exocervix. J Comp Pathol 95:335–344
StruyfF.,
PlateA. E.,
SpearP. G.2005; Deletion of the second immunoglobulin-like domain of nectin-1 alters its intracellular processing and localization and ability to mediate entry of herpes simplex virus. J Virol 79:3841–3845
TakaiY.,
IrieK.,
ShimizuK.,
SakisakaT.,
IkedaW.2003; Nectins and nectin-like molecules: roles in cell adhesion, migration, and polarization. Cancer Sci 94:655–667
TakaishiK.,
SasakiT.,
KotaniH.,
NishiokaH.,
TakaiY.1997; Regulation of cell-cell adhesion by Rac and Rho small G proteins in MDCK cells. J Cell Biol 139:1047–1059
TamJ. E.,
KnightS. T.,
DavisC. H.,
WyrickP. B.1992; Eukaryotic cells grown on microcarrier beads offer a cost-efficient way to propagate Chlamydia trachomatis . Biotechniques 13:374–378
TerresA. M.,
PajaresJ. M.,
O'TooleD.,
AhernS.,
KelleherD.1998; H. pylori infection is associated with downregulation of E-cadherin, a molecule involved in epithelial cell adhesion and proliferation control. J Clin Pathol 51:410–412
YingS.,
SeiffertB. M.,
HackerG.,
FischerS. F.2005; Broad degradation of proapoptotic proteins with the conserved Bcl-2 homology domain 3 during infection with Chlamydia trachomatis . Infect Immun 73:1399–1403
ZhongG.,
FanT.,
LiuL.1999; Chlamydia inhibits interferon γ -inducible major histocompatibility complex class II expression by degradation of upstream stimulatory factor 1. J Exp Med 189:1931–1938
ZhongG.,
LiuL.,
FanT.,
FanP.,
JiH.2000; Degradation of transcription factor RFX5 during the inhibition of both constitutive and interferon γ -inducible major histocompatibility complex class I expression in chlamydia-infected cells. J Exp Med 191:1525–1534