title: Pathogen recognition in the human female reproductive tract: expression of intracellular cytosolic sensors NOD1, NOD2, RIG-1, and MDA5 and response to HIV-1 and Neisseria gonorrhea.
abstract: OBJECTIVE
  Expression patterns and regulation of cytosolic pattern recognition receptors (PRR) NOD-1, NOD-2, RIG-1, and MDA5 have not been elucidated in the human female reproductive tract (FRT).
  
  
  METHODS
  Primary epithelial cells (EC) isolated from Fallopian tube (FT), endometrium (EM), cervix (Cx), and ectocervix (Ecx) were treated with estradiol, poly(I:C), Neisseria gonorrhea (GC), and HIV-1. PRR mRNA expressions were analyzed by Real-time RT-PCR. Conditioned media were analyzed for IL-8 by ELISA.
  
  
  RESULTS
  EC from all FRT compartments constitutively expressed NOD1, NOD2, RIG-1, and MDA5 with highest levels expressed by FT. Stimulation with poly(I:C) resulted in upregulation of NOD2, RIG-1, and MDA5 in all FRT compartments and correlated with increased secretion of IL-8, whereas estradiol treatment had no effects. Exposure to GC and HIV-1 IIIB but not BaL resulted in selective upregulation of NOD2 and MDA5.
  
  
  CONCLUSIONS
  PRR are expressed throughout the FRT and differentially regulated by poly(I:C), GC and HIV-1.
authors.affiliation: Department of Epidemiology and Biostatistics, The George Washington University, Washington, DC 20037, USA. mghosh@gwu.edu
authors.forename: Mimi
authors.initials: M
authors.lastname: Ghosh
authors.forename: Zheng
authors.initials: Z
authors.lastname: Shen
authors.forename: John V
authors.initials: JV
authors.lastname: Fahey
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Crist
authors.forename: Mickey
authors.initials: M
authors.lastname: Patel
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Smith
authors.forename: Charles R
authors.initials: CR
authors.lastname: Wira
mesh_terms: D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D004958:Estradiol / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D005836:Genitalia, Female / Q000276:immunology* / Q000382:microbiology; D006069:Gonorrhea / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D016209:Interleukin-8 / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D060737:Reproductive Tract Infections / Q000276:immunology*
chemical_list: D016209:Interleukin-8; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; D004958:Estradiol; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C