PUBLICATION

Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae

Authors
Chang, M.Y., Cheng, Y.C., Hsu, S.H., Ma, T.L., Chou, L.F., Hsu, H.H., Tian, Y.C., Chen, Y.C., Sun, Y.J., Hung, C.C., Pan, R.L., Yang, C.W.
ID
ZDB-PUB-160610-4
Date
2016
Source
Scientific Reports   6: 27838 (Journal)
Registered Authors
Keywords
Interstitial nephritis, Pathogens
MeSH Terms
  • Zebrafish*/embryology
  • Zebrafish*/microbiology
  • Leptospira/genetics
  • Leptospira/metabolism*
  • Kidney*/embryology
  • Kidney*/microbiology
  • Animals
  • Lipoproteins/genetics
  • Lipoproteins/metabolism*
  • Pronephros*/embryology
  • Pronephros*/microbiology
  • Kidney Diseases*/embryology
  • Kidney Diseases*/genetics
  • Kidney Diseases*/microbiology
  • Inflammation/embryology
  • Inflammation/genetics
  • Inflammation/microbiology
  • Bacterial Outer Membrane Proteins/genetics
  • Bacterial Outer Membrane Proteins/metabolism*
(all 19)
PubMed
27278903 Full text @ Sci. Rep.
Abstract
Leptospirosis is an often overlooked cause of acute kidney injury that can lead to multiple organ failure and even death. The principle protein that conserved in many pathogenic leptospires is the outer membrane protein LipL32. However, the role of LipL32 in the pathogenesis of renal injury in leptospirosis is not entirely clear. Here we studied the effects of LipL32 on the developing kidney in zebrafish larvae. Incubation of zebrafish larvae with Leptospira santarosai serovar Shermani induced acute tubular injury predominantly in the proximal pronephric ducts. Furthermore, microinjection of lipl32 mRNA or recombinant LipL32 protein into zebrafish larvae increased macrophage accumulation and disrupted the basolateral location of NA-K-ATPase in pronephric ducts. These changes led to substantial impairment of the pronephric kidney structure. We further demonstrated that morpholino knockdown of tlr2, but not tlr4, reduced the LipL32-induced leukocyte infiltration and kidney injury. These data demonstrate that LipL32 contributes to the renal pathology in leptospirosis and gives some clues to the potential virulence of LipL32. Our results support the use of zebrafish as a model organism for studying the disease mechanism of leptospiral infection. This model might permit the future exploration of the virulence and molecular pathways of different leptospiral outer membrane proteins.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTbacterial treatment by exposure to environmentLong-pec
WTbacterial treatment by exposure to environmentLong-pec
WTbacterial treatment by exposure to environmentLong-pec
1 - 3 of 3
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
li1TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    Human Disease Fish Conditions Evidence
    leptospirosisWTbacterial treatment by exposure to environmentTAS
    1 - 1 of 1
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    Sequence Targeting Reagents
    Target Reagent Reagent Type
    myd88MO1-myd88MRPHLNO
    tlr2MO1-tlr2MRPHLNO
    tlr2MO2-tlr2MRPHLNO
    tlr4baMO2-tlr4baMRPHLNO
    tlr4bbMO2-tlr4bbMRPHLNO
    1 - 5 of 5
    Show
    Fish
    Fish
    WT
    1 - 1 of 1
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    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab1-atp1amonoclonal
      		IgG1Mouse
      Ab1-mycmonoclonal
        		IgG1Mouse
        Ab3-tubamonoclonal
          		IgG1Mouse
          1 - 3 of 3
          Show
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          1 - 1 of 1
          Show
          Mapping
          No data available
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          Citation
          Chang, M.Y., Cheng, Y.C., Hsu, S.H., Ma, T.L., Chou, L.F., Hsu, H.H., Tian, Y.C., Chen, Y.C., Sun, Y.J., Hung, C.C., Pan, R.L., Yang, C.W. (2016) Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae. Scientific Reports. 6:27838.