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Department of Cell Biology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, Peoples Republic of China
Address all correspondence and requests for reprints to: Daishu Han, Ph.D., Department of Cell Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, Peoples Republic of China. E-mail: dshan{at}ibms.pumc.edu.cn.
Toll-like receptors (TLRs) play crucial roles in mediating innate and adaptive immunity. Sertoli cells create a microenvironment that protects seminiferous tubules from autoantigens and invading pathogens. Here we examined the expression and potential function of TLR family in mouse Sertoli cells. RT-PCR, Western blotting, and flow cytometry were used to analyze gene expression. Immunofluorescence staining was used to determine activation of nuclear factor-
B. ELISA was used to detect secreted cytokines in culture medium. The phagocytosis assay was performed by Oil Red O staining for lipid droplets. We demonstrated that TLR2, TLR3, TLR4, and TLR5 are highly expressed; TLR6, TLR7, and TLR13 are expressed at relatively low level; and TLR1, TLR8, TLR9, TLR11, and TLR12 are not detected in mouse Sertoli cells. We focused our study on the roles of TLR2-TLR5 in Sertoli cells. Our data indicated that TLR2-TLR5 can be activated by their ligands in mouse Sertoli cells and subsequently increase expression of the inflammatory cytokines IL-1
, IL-6, and interferon-
, and -β. The augmented expression of the cytokines might be induced by activation of nuclear factor-
B. Notably, activation of TLR3 by its ligand, poly (I:C), specifically promoted phagocytosis of apoptotic spermatogenic cells by Sertoli cells. The TLR-induced Sertoli cell phagocytosis was found to be associated with the up-regulation of scavenger receptors. The results suggest that TLRs expressed in mouse Sertoli cells may play roles in defense against invasion of allo- and autoantigens in the seminiferous tubules.
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