title: Pattern recognition molecules activated by Chlamydia muridarum infection of cloned murine oviduct epithelial cell lines.
abstract: Chlamydia trachomatis is the most common bacterial sexually transmitted disease in the United States and a major cause of female infertility due to infection-induced Fallopian tube scarring. Epithelial cells are likely central to host defense and pathophysiology as they are the principal cell type productively infected by C. trachomatis. We generated cloned murine oviduct epithelial cell lines without viral or chemical transformation to investigate the role of the TLRs and cytosolic nucleotide binding site/leucine-rich repeat proteins Nod1 and Nod2 in epithelial responses to Chlamydia muridarum infection. RT-PCR assays detected mRNA for TLR2 (TLRs 1 and 6), TLR3, and TLR5. No mRNA was detected for TLRs 4, 7, 8, and 9. Messenger RNAs for Nod1 and Nod2 were present in the epithelial cell lines. Oviduct epithelial cell lines infected with C. muridarum or exposed to the TLR2 agonist peptidoglycan secreted representative acute phase cytokines IL-6 and GM-CSF in a MyD88-dependent fashion. Infected epithelial cell lines secreted the immunomodulatory cytokine IFN-beta, even though C. muridarum does not have a clear pathogen-associated molecular pattern (PAMP) for triggering IFN-beta transcription. The oviduct epithelial lines did not secrete IFN-beta in response to the TLR2 agonist peptidoglycan or to the TLR3 agonist poly(I:C). Our data identify TLR2 as the principal TLR responsible for secretion of acute phase cytokines by C. muridarum-infected oviduct epithelial cell lines. The pattern recognition molecule responsible for infection-induced IFN-beta secretion by oviduct epithelial cells remains to be determined.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Wilbert A
authors.initials: WA
authors.lastname: Derbigny
authors.forename: Micah S
authors.initials: MS
authors.lastname: Kerr
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Johnson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology; D002460:Cell Line; D023502:Chlamydia muridarum / Q000472:pathogenicity*; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005187:Fallopian Tubes / Q000276:immunology* / Q000382:microbiology; D005260:Female; D016899:Interferon-beta / Q000502:physiology; D051379:Mice; D053594:Myeloid Differentiation Factor 88; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D016899:Interferon-beta; D011070:Poly I-C