title: Structural damage in the C. elegans epidermis causes release of STA-2 and induction of an innate immune response.
abstract: The epidermis constantly encounters invasions that disrupt its architecture, yet whether the epidermal immune system utilizes damaged structures as danger signals to activate self-defense is unclear. Here, we used a C. elegans epidermis model in which skin-penetrating infection or injury activates immune defense and antimicrobial peptide (AMP) production. By systemically disrupting each architectural component, we found that only disturbance of the apical hemidesmosomes triggered an immune response and robust AMP expression. The epidermis recognized structural damage through hemidesmosomes associated with a STAT-like protein, whose disruption led to detachment of STA-2 molecules from hemidesmosomes and transcription of AMPs. This machinery enabled the epidermis to bypass certain signaling amplification and directly trigger AMP production when subjected to extensive architectural damage. Together, our findings uncover an evolutionarily conserved mechanism for the epithelial barriers to detect danger and activate immune defense.
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Wenna
authors.initials: W
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Yuanbao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China. Electronic address: sdxiong@suda.edu.cn.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China. Electronic address: zhanghuimin@suda.edu.cn.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics; D017173:Caenorhabditis elegans / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000276:immunology / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002478:Cells, Cultured; D004817:Epidermis / Q000276:immunology* / Q000293:injuries*; D022002:Hemidesmosomes / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; C432913:MUP-4 protein, C elegans; C000597425:STA-2 protein, C elegans; D050791:STAT Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases