title: The Gram-negative bacterium Chlamydia trachomatis L2 stimulates tumor necrosis factor secretion by innate immune cells independently of its endotoxin.
abstract: The endotoxin of Chlamydia trachomatis L(2), the causative agent of lymphogranuloma venerum, has been described as an endotoxin with an atypical structure and weak stimulatory activity. It is, however, unclear whether chlamydial endotoxin plays a role in the stimulation of innate immune cells upon contact with the whole microorganism C. trachomatis L(2). We show here that chlamydial endotoxin and, as expected, Escherichia coli O55:B5 endotoxin depend on Toll-like receptor 4 without depending on Toll-like receptor 2 to stimulate bone marrow-derived dendritic cells to secrete tumor necrosis factor (TNF). In contrast, the whole microorganism C. trachomatis L(2) induces TNF secretion by innate immune cells independently of Toll-like receptor 4, while stimulation by E. coli O55:B5 depends on Toll-like receptor 4. Furthermore, although TNF secretion of the macrophage cell line RAW264.7 with chlamydial or E. coli O55:B5 endotoxin as well as with the bacterium E. coli O55:B5 is inhibited by the endotoxin-neutralizing compound polymyxin B, C. trachomatis L(2)-induced secretion of TNF cannot be reduced. In accordance with the literature, the potential of chlamydial endotoxin is more than 100-fold weaker than E. coli O55:B5 endotoxin on all cell types tested. We conclude that chlamydial endotoxin is unlikely to be involved in C. trachomatis L(2)-induced release of TNF by innate immune cells.
authors.affiliation: Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstr. 9, 81675 Munich, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Prebeck
authors.forename: Helmut
authors.initials: H
authors.lastname: Brade
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Clarissa Prazeres
authors.initials: CP
authors.lastname: da Costa
authors.forename: Susanne
authors.initials: S
authors.lastname: Dürr
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Thomas
authors.initials: T
authors.lastname: Miethke
mesh_terms: D000818:Animals; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000737:chemistry / Q000502:physiology*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000502:physiology; D007113:Immunity, Innate / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011112:Polymyxin B / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B