title: Toll-like receptor-2, but not Toll-like receptor-4, is essential for development of oviduct pathology in chlamydial genital tract infection.
abstract: The roles of Toll-like receptor (TLR) 2 and TLR4 in the host inflammatory response to infection caused by Chlamydia trachomatis have not been elucidated. We examined production of TNF-alpha and IL-6 in wild-type TLR2 knockout (KO), and TLR4 KO murine peritoneal macrophages infected with the mouse pneumonitis strain of C. trachomatis. Furthermore, we compared the outcomes of genital tract infection in control, TLR2 KO, and TLR4 KO mice. Macrophages lacking TLR2 produced significantly less TNF-alpha and IL6 in response to active infection. In contrast, macrophages from TLR4 KO mice consistently produced higher TNF-alpha and IL-6 responses than those from normal mice on in vitro infection. Infected TLR2-deficient fibroblasts had less mRNA for IL-1, IL-6, and macrophage-inflammatory protein-2, but TLR4-deficient cells had increased mRNA levels for these cytokines compared with controls, suggesting that ligation of TLR4 by whole chlamydiae may down-modulate signaling by other TLRs. In TLR2 KO mice, although the course of genital tract infection was not different from that of controls, significantly lower levels of TNF-alpha and macrophage-inflammatory protein-2 were detected in genital tract secretions during the first week of infection, and there was a significant reduction in oviduct and mesosalpinx pathology at late time points. TLR4 KO mice responded to in vivo infection similarly to wild-type controls and developed similar pathology. TLR2 is an important mediator in the innate immune response to C. trachomatis infection and appears to play a role in both early production of inflammatory mediators and development of chronic inflammatory pathology.
authors.affiliation: Division of Pediatric Infectious Diseases, Arkansas Children's Hospital and University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA. darvilletonil@uams.edu
authors.forename: Toni
authors.initials: T
authors.lastname: Darville
authors.forename: Joshua M
authors.initials: JM
authors.lastname: O'Neill
authors.forename: Charles W
authors.initials: CW
authors.lastname: Andrews
authors.forename: Uma M
authors.initials: UM
authors.lastname: Nagarajan
authors.forename: Lynn
authors.initials: L
authors.lastname: Stahl
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002692:Chlamydia trachomatis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005187:Fallopian Tubes / Q000276:immunology / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005831:Genital Diseases, Female / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha