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Cadmium disrupts the immune antibacterial function of the freshwater crab Sinopotamon henanense via the Toll/proPO-AS pathway.

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Τίτλος: Cadmium disrupts the immune antibacterial function of the freshwater crab Sinopotamon henanense via the Toll/proPO-AS pathway.
Συγγραφείς: Liang Y; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China., Pei D; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China., Liu C; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China., Yan F; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China., Bao M; School of Life Science, Shanxi Normal University, Taiyuan, Shanxi Province 030031, China., Liu N; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China., Wang Q; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China., Feng C; Department of Biological and Food Engineering, Lyuliang University, Shanxi Province 033001, China., Jia R; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China. Electronic address: sxdxjiaru@sxu.edu.cn., Wang L; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China. Electronic address: lanwang@sxu.edu.cn.
Πηγή: Journal of hazardous materials [J Hazard Mater] 2026 Aug 01; Vol. 514, pp. 142826. Date of Electronic Publication: 2026 Jun 27.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9422688 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3336 (Electronic) Linking ISSN: 03043894 NLM ISO Abbreviation: J Hazard Mater Subsets: MEDLINE
Imprint Name(s): Original Publication: Amsterdam : Elsevier
Ιατρικοί όροι (MeSH): Brachyura*/immunology , Brachyura*/drug effects , Brachyura*/microbiology , Cadmium*/toxicity , Catechol Oxidase*/metabolism , Enzyme Precursors*/metabolism , Toll-Like Receptors*/metabolism , Water Pollutants, Chemical*/toxicity , Aeromonas hydrophila*, Signal Transduction/drug effects ; Immunity, Innate/drug effects ; Animals
Περίληψη: Cadmium (Cd) is a harmful pollutant commonly found in rivers near mining areas, which can interfere with the immune system of freshwater organisms. Furthermore, its combined exposure with pathogens exhibits synergistic toxic effects. To explore the immunotoxic mechanism of Cd and Aeromonas hydrophila on the freshwater crab Sinopotamon henanense, this study constructed a dual stress model to investigate the regulatory role of prophenoloxidase activation system (proPO-AS) and Toll pathways in Cd-mediated immunotoxicity. The results showed that Cd disrupted downstream nuclear transcriptional regulatory nodes of the Toll pathway by inhibiting the expression and nuclear translocation of ShDorsal and upregulating ShCactus expression. Meanwhile, Cd impaired the proPO-AS by affecting ShPpae function, thereby reducing host's anti-infective capacity. This study proposes for the first time the ShPpae-ShDorsal-ShCactus axis as a functional hub connecting proPO-AS and Toll pathways, enabling a dual protection mechanism of "rapid innate-effector function + sustained transcription-dependent defense". Upon single challenge with 1/4 LD50A. hydrophila for 24 h or exposure to 7.25 mg/L CdCl₂ for 7 days, ShPpae activated melanization after cellular entry, while ShCactus degradation promoted ShDorsal nuclear translocation and induced Shalf6 expression. In contrast, under 29 mg/L CdCl2 single exposure for 7 days or combined Cd-bacterial challenge, the expression and subcellular redistribution of ShPpae were inhibited, and the abnormal upregulation of ShCactus led to tight binding with ShDorsal and blocked its nuclear entry, thereby suppressing the transcription of AMPs. This work reveals a theoretical basis for elucidating the immune regulatory rules of aquatic organisms under combined heavy metal-pathogen stress and enriching the research on heavy metal immunotoxicity.
(Copyright © 2026. Published by Elsevier B.V.)
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Aeromonas hydrophila; Cadmium; Prophenoloxidase-activating system; Sinopotamon henanense; Toll signaling pathway
Substance Nomenclature: 00BH33GNGH (Cadmium)
EC 1.10.3.1 (Catechol Oxidase)
EC 1.10.3.- (pro-phenoloxidase)
0 (Enzyme Precursors)
0 (Toll-Like Receptors)
0 (Water Pollutants, Chemical)
Entry Date(s): Date Created: 20260707 Date Completed: 20260725 Latest Revision: 20260725
Update Code: 20260725
DOI: 10.1016/j.jhazmat.2026.142826
PMID: 42413402
Βάση Δεδομένων: MEDLINE
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  Data: Cadmium disrupts the immune antibacterial function of the freshwater crab Sinopotamon henanense via the Toll/proPO-AS pathway.
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  Data: <searchLink fieldCode="AU" term="%22Liang+Y%22">Liang Y</searchLink>; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China.<br /><searchLink fieldCode="AU" term="%22Pei+D%22">Pei D</searchLink>; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China.<br /><searchLink fieldCode="AU" term="%22Liu+C%22">Liu C</searchLink>; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China.<br /><searchLink fieldCode="AU" term="%22Yan+F%22">Yan F</searchLink>; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China.<br /><searchLink fieldCode="AU" term="%22Bao+M%22">Bao M</searchLink>; School of Life Science, Shanxi Normal University, Taiyuan, Shanxi Province 030031, China.<br /><searchLink fieldCode="AU" term="%22Liu+N%22">Liu N</searchLink>; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China.<br /><searchLink fieldCode="AU" term="%22Wang+Q%22">Wang Q</searchLink>; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China.<br /><searchLink fieldCode="AU" term="%22Feng+C%22">Feng C</searchLink>; Department of Biological and Food Engineering, Lyuliang University, Shanxi Province 033001, China.<br /><searchLink fieldCode="AU" term="%22Jia+R%22">Jia R</searchLink>; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China. Electronic address: sxdxjiaru@sxu.edu.cn.<br /><searchLink fieldCode="AU" term="%22Wang+L%22">Wang L</searchLink>; School of Life Science, Shanxi University, Taiyuan, Shanxi Province 030006, China. Electronic address: lanwang@sxu.edu.cn.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Elsevier%22">Elsevier </searchLink><i>Country of Publication: </i>Netherlands <i>NLM ID: </i>9422688 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1873-3336 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2203043894%22">03043894 </searchLink><i>NLM ISO Abbreviation: </i>J Hazard Mater <i>Subsets: </i>MEDLINE
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  Data: <searchLink fieldCode="MM" term="%22Brachyura%22">Brachyura*</searchLink>/<searchLink fieldCode="MM" term="%22Brachyura+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Brachyura%22">Brachyura*</searchLink>/<searchLink fieldCode="MM" term="%22Brachyura+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Brachyura%22">Brachyura*</searchLink>/<searchLink fieldCode="MM" term="%22Brachyura+microbiology%22">microbiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Cadmium%22">Cadmium*</searchLink>/<searchLink fieldCode="MM" term="%22Cadmium+toxicity%22">toxicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Catechol+Oxidase%22">Catechol Oxidase*</searchLink>/<searchLink fieldCode="MM" term="%22Catechol+Oxidase+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Enzyme+Precursors%22">Enzyme Precursors*</searchLink>/<searchLink fieldCode="MM" term="%22Enzyme+Precursors+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Toll-Like+Receptors%22">Toll-Like Receptors*</searchLink>/<searchLink fieldCode="MM" term="%22Toll-Like+Receptors+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Water+Pollutants%2C+Chemical%22">Water Pollutants, Chemical*</searchLink>/<searchLink fieldCode="MM" term="%22Water+Pollutants%2C+Chemical+toxicity%22">toxicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Aeromonas+hydrophila%22">Aeromonas hydrophila*</searchLink><br /><searchLink fieldCode="MH" term="%22Signal+Transduction%22">Signal Transduction</searchLink>/<searchLink fieldCode="MH" term="%22Signal+Transduction+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Immunity%2C+Innate%22">Immunity, Innate</searchLink>/<searchLink fieldCode="MH" term="%22Immunity%2C+Innate+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Cadmium (Cd) is a harmful pollutant commonly found in rivers near mining areas, which can interfere with the immune system of freshwater organisms. Furthermore, its combined exposure with pathogens exhibits synergistic toxic effects. To explore the immunotoxic mechanism of Cd and Aeromonas hydrophila on the freshwater crab Sinopotamon henanense, this study constructed a dual stress model to investigate the regulatory role of prophenoloxidase activation system (proPO-AS) and Toll pathways in Cd-mediated immunotoxicity. The results showed that Cd disrupted downstream nuclear transcriptional regulatory nodes of the Toll pathway by inhibiting the expression and nuclear translocation of ShDorsal and upregulating ShCactus expression. Meanwhile, Cd impaired the proPO-AS by affecting ShPpae function, thereby reducing host's anti-infective capacity. This study proposes for the first time the ShPpae-ShDorsal-ShCactus axis as a functional hub connecting proPO-AS and Toll pathways, enabling a dual protection mechanism of "rapid innate-effector function + sustained transcription-dependent defense". Upon single challenge with 1/4 LD<subscript>50</subscript>A. hydrophila for 24 h or exposure to 7.25 mg/L CdCl₂ for 7 days, ShPpae activated melanization after cellular entry, while ShCactus degradation promoted ShDorsal nuclear translocation and induced Shalf6 expression. In contrast, under 29 mg/L CdCl<subscript>2</subscript> single exposure for 7 days or combined Cd-bacterial challenge, the expression and subcellular redistribution of ShPpae were inhibited, and the abnormal upregulation of ShCactus led to tight binding with ShDorsal and blocked its nuclear entry, thereby suppressing the transcription of AMPs. This work reveals a theoretical basis for elucidating the immune regulatory rules of aquatic organisms under combined heavy metal-pathogen stress and enriching the research on heavy metal immunotoxicity.<br /> (Copyright © 2026. Published by Elsevier B.V.)
– Name: Abstract
  Label: Competing Interests
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  Data: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Aeromonas hydrophila; Cadmium; Prophenoloxidase-activating system; Sinopotamon henanense; Toll signaling pathway
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 00BH33GNGH (Cadmium)<br />EC 1.10.3.1 (Catechol Oxidase)<br />EC 1.10.3.- (pro-phenoloxidase)<br />0 (Enzyme Precursors)<br />0 (Toll-Like Receptors)<br />0 (Water Pollutants, Chemical)
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  Data: <i>Date Created: </i>20260707 <i>Date Completed: </i>20260725 <i>Latest Revision: </i>20260725
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        Text: English
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      – SubjectFull: Signal Transduction drug effects
        Type: general
      – SubjectFull: Immunity, Innate drug effects
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Brachyura immunology
        Type: general
      – SubjectFull: Brachyura drug effects
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      – SubjectFull: Aeromonas hydrophila
        Type: general
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      – TitleFull: Cadmium disrupts the immune antibacterial function of the freshwater crab Sinopotamon henanense via the Toll/proPO-AS pathway.
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              Text: 2026 Aug 01
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