Toll-like receptor 3 activation induces antiviral immune responses in mouse sertoli cells.
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and elicit antimicrobial immune responses. In the testis, viruses can induce pathological conditions, such as orchitis, and may participate in the etiology of testicular cancer; however, the molecular mechanisms involved remain under investigation. It has been suggested that because they constitutively express interferon (IFN)-inducible antiviral proteins, Sertoli cells participate in the testicular antiviral defense system. Previously, we demonstrated a key function of mouse Sertoli cells in the bactericidal testicular defense mechanism mediated by a panel of TLRs. To better characterize the potential role of Sertoli cells in the response against testicular viral infections, we investigated the TLR3 expression and function in these cells. Sertoli cells express TLR3, and under stimulation with the synthetic double-stranded RNA analogue poly (I:C), they produce the proinflammatory molecule ICAM1 and secrete functionally active CCL2 chemokine. Using both pharmacological and genetic approaches, we found that these effects are TLR3-dependent. Moreover, using ELISA, we found that IFNA is constitutively produced and not further inducible, whereas IFNB1 is absent and dramatically induced only by transfected poly (I:C), indicating different control mechanisms underlying IFNA and IFNB1 production. To conclude, poly (I:C) elicits both inflammatory and antiviral responses in Sertoli cells.
Starace
Donatella
D
Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.
Galli
Roberta
R
Paone
Alessio
A
De Cesaris
Paola
P
Filippini
Antonio
A
Ziparo
Elio
E
Riccioli
Anna
A
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects* / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D012708:Sertoli Cells / Q000187:drug effects* / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D014780:Viruses / Q000276:immunology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D016328:NF-kappa B; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D018799:Intercellular Adhesion Molecule-1; D048049:Extracellular Signal-Regulated MAP Kinases; D011070:Poly I-C