title: Sertoli cells have a functional NALP3 inflammasome that can modulate autophagy and cytokine production.
abstract: Sertoli cells, can function as non-professional tolerogenic antigen-presenting cells, and sustain the blood-testis barrier formed by their tight junctions. The NOD-like receptor family members and the NALP3 inflammasome play a key role in pro-inflammatory innate immunity signalling pathways. Limited data exist on NOD1 and NOD2 expression in human and mouse Sertoli cells. Currently, there is no data on inflammasome expression or function in Sertoli cells. We found that in primary pre-pubertal Sertoli cells and in adult Sertoli line, TLR4\NOD1 and NOD2 crosstalk converged in NFκB activation and elicited a NALP3 activation, leading to de novo synthesis and inflammasome priming. This led to caspase-1 activation and IL-1β secretion. We demonstrated this process was controlled by mechanisms linked to autophagy. NOD1 promoted pro-IL-1β restriction and autophagosome maturation arrest, while NOD2 promoted caspase-1 activation, IL-1β secretion and autophagy maturation. NALP3 modulated NOD1 and pro-IL-1β expression, while NOD2 inversely promoted IL-1β. This study is proof of concept that Sertoli cells, upon specific stimulation, could participate in male infertility pathogenesis via inflammatory cytokine induction.
authors.affiliation: Institute of Biology and Immunology of Reproduction, Laboratory of Reproductive Omics Technologies, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Soren
authors.initials: S
authors.lastname: Hayrabedyan
authors.affiliation: Institute of Biology and Immunology of Reproduction, Laboratory of Reproductive Omics Technologies, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Krassimira
authors.initials: K
authors.lastname: Todorova
authors.affiliation: School of Biological Sciences, Wivenhoe Park, University of Essex, Colchester, UK.
authors.forename: Asma
authors.initials: A
authors.lastname: Jabeen
authors.affiliation: School of Biological Sciences, Wivenhoe Park, University of Essex, Colchester, UK.
authors.forename: Gergana
authors.initials: G
authors.lastname: Metodieva
authors.affiliation: Cellular and Gene Therapy Ward, National Specialized Haematology Hospital, Sofia, Bulgaria.
authors.forename: Stavri
authors.initials: S
authors.lastname: Toshkov
authors.affiliation: School of Biological Sciences, Wivenhoe Park, University of Essex, Colchester, UK.
authors.forename: Metodi V
authors.initials: MV
authors.lastname: Metodiev
authors.affiliation: Cellular and Gene Therapy Ward, National Specialized Haematology Hospital, Sofia, Bulgaria.
authors.forename: Milcho
authors.initials: M
authors.lastname: Mincheff
authors.affiliation: School of Biological Sciences, Wivenhoe Park, University of Essex, Colchester, UK.
authors.forename: Nelson
authors.initials: N
authors.lastname: Fernández
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D001343:Autophagy / Q000235:genetics / Q000276:immunology; D001814:Blood-Testis Barrier / Q000276:immunology; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics* / Q000276:immunology; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D012708:Sertoli Cells / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D020170:Caspase 1