title: Synergic activation of toll-like receptor (TLR) 2/6 and 9 in response to Ureaplasma parvum & urealyticum in human amniotic epithelial cells.
abstract: Ureaplasma species are the most frequently isolated microorganisms inside the amniotic cavity and have been associated with spontaneous abortion, chorioamnionitis, premature rupture of the membranes (PROM), preterm labour (PL) pneumonia in neonates and bronchopulmonary dysplasia in neonates. The mechanisms by which Ureaplasmas cause such diseases remain unclear, but it is believed that inappropriate induction of inflammatory responses is involved, triggered by the innate immune system. As part of its mechanism of activation, the innate immune system employs germ-lined encoded receptors, called pattern recognition receptors (PRRs) in order to "sense" pathogens. One such family of PRRs are the Toll like receptor family (TLR). In the current study we aimed to elucidate the role of TLRs in Ureaplasma-induced inflammation in human amniotic epithelial cells. Using silencing, as well as human embryonic kidney (HEK) transfected cell lines, we demonstrate that TLR2, TLR6 and TLR9 are involved in the inflammatory responses against Ureaplasma parvum and urealyticum serovars. Ureaplasma lipoproteins, such as Multiple Banded antigen (MBA), trigger responses via TLR2/TLR6, whereas the whole bacterium is required for TLR9 activation. No major differences were observed between the different serovars. Cell activation by Ureaplasma parvum and urealyticum seem to require lipid raft function and formation of heterotypic receptor complexes comprising of TLR2 and TLR6 on the cell surface and TLR9 intracellularly.
authors.affiliation: Department of Child Health, School of Medicine, University Hospital of Wales, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors.forename: Martha
authors.initials: M
authors.lastname: Triantafilou
authors.forename: Benjamin
authors.initials: B
authors.lastname: De Glanville
authors.forename: Ali F
authors.initials: AF
authors.lastname: Aboklaish
authors.forename: O Brad
authors.initials: OB
authors.lastname: Spiller
authors.forename: Sailesh
authors.initials: S
authors.lastname: Kotecha
authors.forename: Kathy
authors.initials: K
authors.lastname: Triantafilou
mesh_terms: D000650:Amnion / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000382:microbiology; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D031541:Fluorescence Resonance Energy Transfer; D005677:G(M1) Ganglioside / Q000378:metabolism; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000382:microbiology; D021962:Membrane Microdomains / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014509:Ureaplasma / Q000502:physiology*; D016869:Ureaplasma Infections / Q000378:metabolism* / Q000382:microbiology; D016990:Ureaplasma urealyticum / Q000502:physiology*
chemical_list: D016207:Cytokines; D053594:Myeloid Differentiation Factor 88; C495342:TLR2 protein, human; C495368:TLR6 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D005677:G(M1) Ganglioside