title: Sertoli cells initiate testicular innate immune responses through TLR activation.
abstract: TLRs play a crucial role in early host defense against invading pathogens. In the seminiferous epithelium, Sertoli cells are the somatic nurse cells that mechanically segregate germ cell autoantigens by means of the blood-tubular barrier and create a microenvironment that protects germ cells from both interstitial and ascending invading pathogens. The objective of this study was to examine TLR expression and their functional responses to specific agonists in mouse Sertoli cells. We measured the expression of TLR2, TLR4, TLR5, and TLR6 mRNAs and confirmed by FACS analysis the presence of proteins TLR2 and TLR5 on which we focused our study. Stimulation of Sertoli cells with macrophage-activating lipopeptide-2, agonist of TLR2/TLR6, and with flagellin, agonist of TLR5, induces augmented secretion of the chemokine MCP-1. To assess the functional significance of MCP-1 production following TLR stimulation, conditioned medium from either macrophage-activating lipopeptide-2 or flagellin-treated Sertoli cells was tested for in vitro chemotaxis assay, and a significant increase of macrophage migration was observed in comparison with unstimulated conditioned medium. Moreover, we studied the role of NF-kappaB and of MAPKs in regulating TLR-mediated MCP-1 secretion by using inhibitors specific for each transduction pathway and we demonstrated a pivotal role of the IkappaB/NF-kappaB and JNK systems. In addition, TLR2/TLR6 and TLR5 stimulation induces increased ICAM-1 expression in Sertoli cells. Collectively, this study demonstrates the novel ability of Sertoli cells to potentially respond to a wide variety of bacteria through TLR stimulation.
authors.affiliation: Department of Histology and Medical Embryology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome La Sapienza, Rome, Italy. anna.riccioli@uniroma1.it
authors.forename: Anna
authors.initials: A
authors.lastname: Riccioli
authors.forename: Donatella
authors.initials: D
authors.lastname: Starace
authors.forename: Roberta
authors.initials: R
authors.lastname: Galli
authors.forename: Andrea
authors.initials: A
authors.lastname: Fuso
authors.forename: Sigfrido
authors.initials: S
authors.lastname: Scarpa
authors.forename: Fioretta
authors.initials: F
authors.lastname: Palombi
authors.forename: Paola
authors.initials: P
authors.lastname: De Cesaris
authors.forename: Elio
authors.initials: E
authors.lastname: Ziparo
authors.forename: Antonio
authors.initials: A
authors.lastname: Filippini
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D005408:Flagellin / Q000494:pharmacology; D007113:Immunity, Innate; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D055666:Lipopeptides; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009842:Oligopeptides / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012671:Seminiferous Tubules / Q000276:immunology / Q000378:metabolism; D012708:Sertoli Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D055666:Lipopeptides; D016328:NF-kappa B; D009842:Oligopeptides; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D018799:Intercellular Adhesion Molecule-1; D005408:Flagellin; C106335:macrophage stimulatory lipopeptide 2; D020928:Mitogen-Activated Protein Kinases