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BOR - Papers in Press, published online ahead of print July 2, 2008.
Biol Reprod 2008, 10.1095/biolreprod.108.068619
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BIOLOGY OF REPRODUCTION 79, 766–775 (2008)
DOI: 10.1095/biolreprod.108.068619
© 2008 by the Society for the Study of Reproduction, Inc.

Toll-Like Receptor 3 Activation Induces Antiviral Immune Responses in Mouse Sertoli Cells1

Donatella Starace 3, Roberta Galli 3, Alessio Paone 3, Paola De Cesaris 4, Antonio Filippini 2 3, Elio Ziparo 3, and Anna Riccioli 3

Istituto Pasteur-Fondazione Cenci Bolognetti,3 Department of Histology and Medical Embryology, "Sapienza" University of Rome, 00161 Rome, Italy Department of Experimental Medicine,4 University of L'Aquila, 67100 L'Aquila, Italy

ABSTRACT

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.

cell surface molecules, chemokines, cytokines, immunology, mouse, Sertoli cells, signal transduction, testis, toll-like receptors, type I interferons


FOOTNOTES

1Supported by grants from MIUR PRIN 2007 and ASI: I/061/06/0.

Correspondence: 2Correspondence: Antonio Filippini, Department of Histology and Medical Embryology, "Sapienza" University of Rome, 00161 Rome, Italy. FAX: 39 06 446 2854; e-mail: antonio.filippini{at}uniroma1.it







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Copyright © 2008 by the Society for the Study of Reproduction.