title: Differences in innate immune responses (in vitro) to HeLa cells infected with nondisseminating serovar E and disseminating serovar L2 of Chlamydia trachomatis.
abstract: The inflammatory response associated with Chlamydia trachomatis genital infections is thought to be initiated by the release of proinflammatory cytokines from infected epithelial cells. This study focuses on the interactions between C. trachomatis-infected HeLa cells and immune cells involved in the early stages of infection, i.e., neutrophils and macrophages. First, we showed that the expression of interleukin-11 (IL-11), an anti-inflammatory cytokine mainly active on macrophages, was upregulated at the mRNA level in the genital tracts of infected mice. Second, incubation of differentiated THP-1 (dTHP-1) cells or monocyte-derived macrophages (MdM) with basal culture supernatants from C. trachomatis serovar E- or serovar L2-infected HeLa cells resulted in macrophage activation with a differential release of tumor necrosis factor alpha (TNF-alpha) and upregulation of indoleamine 2,3-deoxygenase (IDO) but not of Toll-like receptor 2 and 4 mRNA expression. Third, coculture of infected HeLa cells with dTHP-1 cells resulted in a reduction in chlamydial growth, which was more dramatic for serovar E than for L2 and which was partially reversed by the addition of anti-TNF-alpha antibodies for serovar E or exogenous tryptophan for both serovars but was not reversed by the addition of superoxide dismutase or anti-IL-8 or anti-IL-1beta antibodies. A gamma interferon-independent IDO mRNA upregulation was also detected in dTHP-1 cells from infected cocultures. Lastly, with a two-stage coculture system, we found that (i) supernatants from neutrophils added to the apical side of infected HeLa cell cultures were chlamydicidal and induced MdM to express antichlamydial activity and (ii) although polymorphonuclear leukocytes released more proinflammatory cytokines in response to serovar E- than in response to L2-infected cells, MdM were strongly activated by serovar L2 infection, indicating that the early inflammatory response generated with a nondisseminating or a disseminating strain is different.
authors: Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37684, USA.
authors: Sophie
authors: S
authors: Dessus-Babus
authors: Toni L
authors: TL
authors: Darville
authors: Francis P
authors: FP
authors: Cuozzo
authors: Kaethe
authors: K
authors: Ferguson
authors: Priscilla B
authors: PB
authors: Wyrick
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000254:growth & development / Q000276:immunology*; D018920:Coculture Techniques; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017370:Interleukin-11 / Q000235:genetics; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology*; D012333:RNA, Messenger; D011956:Receptors, Cell Surface / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014366:Tryptophan Oxygenase / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D003470:Culture Media; D016207:Cytokines; D029721:Drosophila Proteins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017370:Interleukin-11; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D014366:Tryptophan Oxygenase