Testicular innate immune defense against bacteria

Bhushan, Sudhanshu; Schuppe, Hans‐Christian; Tchatalbachev, Svetlin; Fijak, Monika; Weidner, W.; Chakraborty, Trinad; Meinhardt, Andreas

doi:10.1016/j.mce.2008.10.017

Cited by 32 publications

(25 citation statements)

References 94 publications

(95 reference statements)

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“…We consider that this could be important for preserving the integrity and the function of epithelia from excessive or prolonged inflammation caused by PAMPs in those tissues where S5D-SRCRB is expressed. This is best exemplified by the expression of mouse S5D-SRCRB in seminiferous testicular tubules, where infection and inflammation may cause male infertility, thus compromising murine reproductive capability (36). The expression of mouse S5D-SRCRB in these tissues also argues in favor of its putative FIGURE 7.…”

Section: Discussionmentioning

confidence: 99%

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

Miró-Julià

Roselló

Martínez

et al. 2011

The Journal of Immunology

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The scavenger receptor cysteine-rich superfamily (SRCR-SF) members are transmembrane and/or secreted receptors exhibiting one or several repeats of a cysteine-rich protein module of ∼100 aa, named scavenger receptor cysteine-rich (SRCR). Two types of SRCR domains (A or B) have been reported, which differ in the number of coding exons and intradomain cysteines. Although no unifying function has been reported for SRCR-SF members, recognition of pathogen-associated molecular patterns (PAMPs) was recently shown for some of them. In this article, we report the structural and functional characterization of mouse S5D-SRCRB, a new group B member of the SRCR-SF. The s5d-srcrb gene maps at mouse chromosome 7 and encompasses 14 exons extending over 15 kb. The longest cDNA sequence found is 4286 bp in length and encodes a mature protein of 1371 aa, with a predicted Mr of 144.6 kDa. Using an episomal mammalian-expression system, a glycosylated soluble recombinant form >200 kDa was obtained and used as immunogen for the generation of specific rat mAbs. Subsequent immunohistochemical and real-time PCR analysis showed significant S5D-SRCRB expression in murine genitourinary and digestive tracts. S5D-SRCRB was shown to bind endogenous extracellular matrix proteins (laminin and galectin-1), as well as PAMPs present on Gram-positive and Gram-negative bacteria and fungi. PAMP binding by S5D-SRCRB induced microbial aggregation and subsequent inhibition of PAMP-induced cytokine release. These abilities suggest that S5D-SRCRB might play a role in the innate defense and homeostasis of certain specialized epithelial surfaces.

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Section: Discussionmentioning

confidence: 99%

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

Miró-Julià

Roselló

Martínez

et al. 2011

The Journal of Immunology

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“…SCs express several cytokines that can produce proinflammatory and anti-inflammatory effects, as well as numerous other factors that may modulate the immune response; for example, IL1A, IL6, macrophage migration inhibitory factor, IFNA, IFNB, IFNG, TGFB1, activin, C-C motif chemokine ligand 5 (CCL5), CCL2/monocyte chemoattractant protein-1, C-X-C motif chemokine ligand 1 (CXCL1), CXCL10, fractalkine (CX3CL1), and Toll like receptors 2-6 (Hedger & Meinhardt 2003, Bhushan et al 2009, Guazzone et al 2009. It is likely a complex interaction between several immune-modulating molecules may be responsible for SC immunoprotection.…”

Section: Interaction Between Multiple Immune-modulating Factorsmentioning

confidence: 99%

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

Mital¹,

Kaur²,

2010

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The testis as an immune-privileged site allows long-term survival of allogeneic and xenogeneic transplants. Testicular Sertoli cells (SCs) play a major role in this immunoprotection and have been used to create an ectopic immune-privileged environment that prolongs survival of co-transplanted allogeneic and xenogeneic cells, including pancreatic islets and neurons. Extended survival of such grafts testifies to the immunoprotective properties of SCs. However, there is still variability in the survival rates of the co-grafted cells and rarely are 100% of the grafts protected. This emphasizes the need to learn more about what is involved in creating the optimal immunoprotective milieu. Several parameters including organization of the SCs into tubule-like structures and the production of immunomodulatory factors by SCs, specifically complement inhibitors, cytokines, and cytotoxic lymphocyte inhibitors, are likely important. In addition, an intricate interplay between several of these factors may be responsible for providing the most ideal environment for protection of the co-transplants by SCs. In this review, we will also briefly describe a novel use for the immune-privileged abilities of SCs; engineering them to deliver therapeutic proteins for the treatment of diseases like diabetes and Parkinson's disease. In conclusion, further studies and more detailed analysis of the mechanisms involved in creating the immune-protective environment by SCs may make their application in co-transplantation and as engineered cells clinically feasible.

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“…Furthermore, recent studies have reported that mammalian SCs express several TLRs and cytokines that can produce proinflammatory and anti-inflammatory effects (Hedger & Meinhardt 2003, Bhushan et al 2009, Guazzone et al 2009). It has also been reported that mouse SCs express several members of the Tlr family (Riccioli et al 2006), and that stimulation of Tlr2, Tlr3, and Tlr5 by agonists resulted in increased intercellular adhesion molecule 1 (Icam1) and monocyte chemotactic protein 1 (Mcp1) expression, as well as the activation of the NFkB pathway, adding further credential to a central role of the SCs in testicular immunology (Riccioli et al 2006, Starace et al 2008.…”

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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Testicular innate immune defense against bacteria

Cited by 32 publications

References 94 publications

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

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

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