Sertoli Cells Initiate Testicular Innate Immune Responses through TLR Activation

Riccioli, Anna; Starace, Donatella; Galli, Roberta; Fuso, Andrea; Scarpa, Sigfrido; Palombi, Fioretta; Cesaris, Paola De; Ziparo, Elio; Filippini, Antonio

doi:10.4049/jimmunol.177.10.7122

Cited by 106 publications

(123 citation statements)

References 61 publications

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“…Moreover, intracellular DNA sensors have recently emerged. 101 Since the first investigation of TLRs in testicular SCs, 102 several PRRs that initiate the testicular innate immune responses have been described, and their signaling within testicular cells has been documented ( Figure 3). Table 1 shows a summary of the expression and function of PRRs in testicular cells.…”

Section: Testicular Innate Immunitymentioning

confidence: 99%

“…103 Functional TLRs were initially demonstrated within murine SCs, showing that TLR2 and TLR4 signaling can be initiated by their ligands. 102 TLR expression was then further defined in male rat reproductive tracts and testicular cells. 104,105 The functions of more TLRs, including TLR3, TLR5 and TLR6, were investigated in mouse SCs by our group and by other researchers.…”

Section: Tlrs In Testicular Cellsmentioning

confidence: 99%

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Testicular defense systems: immune privilege and innate immunity

et al. 2014

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The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation.

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Section: Testicular Innate Immunitymentioning

confidence: 99%

Section: Tlrs In Testicular Cellsmentioning

confidence: 99%

Testicular defense systems: immune privilege and innate immunity

et al. 2014

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“…The testis is considered an immune-privileged site, and testicular Sertoli cells (SCs) have been identified as key players for conferring this immune privilege (Selawry 1994, Dufour et al 2003. SCs mechanically segregate germ cell autoantigens by means of the blood-tubular barrier and create an effective immune-privileged environment that protects germ cells from invading pathogens (Riccioli et al 2006, Mital et al 2010. Therefore, the protection of germ cells from infections in the seminiferous tubules is of primary importance, because bacterial infections can seriously damage reproductive functions.…”

Section: Introductionmentioning

confidence: 99%

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Michailidis¹,

Anastasiadou²,

Guibert³

et al. 2014

Reproduction

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Sertoli cells (SCs) play an important physiological role in the testis, as they support, nourish, and protect the germ cells. As protection of the developing spermatozoa is an emerging aspect of reproductive physiology, this study examined the expression pattern of innate immune-related genes, including avian b-defensins (AvBDs), Toll-like receptors (TLRs), and cytokines, and investigated the time course of an inflammatory response in rooster SCs triggered by exposure to the bacterial endotoxin lipopolysaccharide (LPS). SCs were isolated from 6-week-old chicken, cultured in vitro, and stimulated with 1 mg/ml LPS at different time courses (0, 6, 12, 24, and 48 h). Data on expression analysis revealed that all ten members of the chicken TLR family, nine members of the AvBD family, as well as eight cytokine genes were expressed in SCs. Quantitative real-time PCR analysis revealed that LPS treatment resulted in significant induction of the expression levels of six TLRs, six AvBDs, and four cytokine genes, while two cytokine genes were downregulated and two other genes were unchanged. The increasing interleukin 1b (IL1b) production was confirmed in the conditioned medium. Furthermore, the phagocytosis of SCs was increased after LPS treatment. In conclusion, these findings provide evidence that SCs express innate immunerelated genes and respond directly to bacterial ligands. These genes represent an important component of the immune system, which could be integrated into semen, and present a distinctive constituent of the protective repertoire of the testis against ascending infections.

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“…In addition, Palladino et al (2007) showed TLR1-9 mRNA and protein in testes, epididymis and vas deferens. Expression of TLR2-6 mRNA in mouse Sertoli cells and subsequent activation of the NF-kB pathway following stimulation with TLR2 and TLR5 agonists were demonstrated by Riccioli et al (2006). Bhushan et al (2008) demonstrated that all testicular cell types expressed mRNAs of one to six TLRs, and, in particular, TLR3 transcription was evident in all testicular cells, suggesting a strong capacity for the recognition of double-stranded viral RNA in the testes.…”

Section: Discussionmentioning

confidence: 97%

Innate immunity in the male genital tract: Chlamydia trachomatis induces keratinocyte-derived chemokine production in prostate, seminal vesicle and epididymis/vas deferens primary cultures

Mackern-Oberti

Maccioni

Breser

et al. 2011

Journal of Medical Microbiology

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Innate immunity in the male genital tract: Chlamydia trachomatis induces keratinocyte-derived chemokine production in prostate, seminal vesicle and epididymis/vas deferens primary cultures Chlamydia trachomatis is an intracellular pathogen that infects mucosal epithelial cells, causing persistent infections. Although chronic inflammation is a hallmark of chlamydial disease, the proinflammatory mechanisms involved are poorly understood. Little is known about how innate immunity in the male genital tract (MGT) responds to C. trachomatis. Toll-like receptors (TLRs) are a family of receptors of the innate immunity that recognize different pathogen-associated molecular patterns (PAMPs) present in bacteria, viruses, yeasts and parasites. The study of TLR expression in the MGT has been poorly investigated. The aim of this work was to investigate the keratinocyte-derived chemokine (KC) response of MGT primary cultures from C57BL/6 mice to C. trachomatis and different PAMPs. KC production by prostate, seminal vesicle and epididymis/ vas deferens cell cultures was determined by ELISA in culture supernatants. TLR2, 3, 4 and 9 agonists induced the production of KC by all MGT primary cultures assayed. In addition, we analysed the host response against C. trachomatis and Chlamydia muridarum. Chlamydial LPS (cLPS) as well as C. trachomatis and C. muridarum infection induced KC secretion by all MGT cell cultures analysed. Differences in KC levels were observed between cultures, suggesting specific sensitivity against pathogens among MGT tissues. Chemokine secretion was observed after stimulation of seminal vesicle cells with TLR agonists, cLPS and C. trachomatis. To our knowledge, this is the first report showing KC production by seminal vesicle cells after stimulation with TLR ligands, C. trachomatis or C. muridarum antigens. These results indicate that different receptors of the innate immunity are present in the MGT. Understanding specific immune responses, both innate and adaptive, against chlamydial infections, mounted in each tissue of the MGT, will be crucial to design new therapeutic approaches where innate and/or adaptive immunity would be targeted.

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Sertoli Cells Initiate Testicular Innate Immune Responses through TLR Activation

Cited by 106 publications

References 61 publications

Testicular defense systems: immune privilege and innate immunity

Testicular defense systems: immune privilege and innate immunity

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Innate immunity in the male genital tract: Chlamydia trachomatis induces keratinocyte-derived chemokine production in prostate, seminal vesicle and epididymis/vas deferens primary cultures

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