PUBLICATION

Characterization of the innate immune response to Streptococcus pneumoniae infection in zebrafish

Authors
Saralahti, A.K., Harjula, S.E., Rantapero, T., Uusi-Mäkelä, M.I.E., Kaasinen, M., Junno, M., Piippo, H., Nykter, M., Lohi, O., Rounioja, S., Parikka, M., Rämet, M.
ID
ZDB-PUB-230110-8
Date
2023
Source
PLoS Genetics   19: e1010586e1010586 (Journal)
Registered Authors
Harjula, Sanna, Rämet, Mika, Saralahti, Anni, Uusi-Mäkelä, Meri
Keywords
none
Datasets
GEO:GSE112433
MeSH Terms
  • Pneumococcal Infections*/genetics
  • Animals
  • Streptococcus pneumoniae/genetics
  • Immunity, Innate/genetics
  • Zebrafish*/genetics
  • Child
  • Aged
  • C-Reactive Protein
  • Humans
(all 9)
PubMed
36622851 Full text @ PLoS Genet.
Abstract
Streptococcus pneumoniae (pneumococcus) is one of the most frequent causes of pneumonia, sepsis and meningitis in humans, and an important cause of mortality among children and the elderly. We have previously reported the suitability of the zebrafish (Danio rerio) larval model for the study of the host-pathogen interactions in pneumococcal infection. In the present study, we characterized the zebrafish innate immune response to pneumococcus in detail through a whole-genome level transcriptome analysis and revealed a well-conserved response to this human pathogen in challenged larvae. In addition, to gain understanding of the genetic factors associated with the increased risk for severe pneumococcal infection in humans, we carried out a medium-scale forward genetic screen in zebrafish. In the screen, we identified a mutant fish line which showed compromised resistance to pneumococcus in the septic larval infection model. The transcriptome analysis of the mutant zebrafish larvae revealed deficient expression of a gene homologous for human C-reactive protein (CRP). Furthermore, knockout of one of the six zebrafish crp genes by CRISPR-Cas9 mutagenesis predisposed zebrafish larvae to a more severe pneumococcal infection, and the phenotype was further augmented by concomitant knockdown of a gene for another Crp isoform. This suggests a conserved function of C-reactive protein in anti-pneumococcal immunity in zebrafish. Altogether, this study highlights the similarity of the host response to pneumococcus in zebrafish and humans, gives evidence of the conserved role of C-reactive protein in the defense against pneumococcus, and suggests novel host genes associated with pneumococcal infection.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
dt2
    		Unknown
    t1
      		Point Mutation
      tpu6
        		Indel
        tpu9GtTransgenic Insertion
          tpu10GtTransgenic Insertion
            tpu11GtTransgenic Insertion
              1 - 6 of 6
              Show
              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              Target Reagent Reagent Type
              crp2CRISPR1-crp2CRISPR
              crp3MO1-crp3MRPHLNO
              1 - 2 of 2
              Show
              Fish
              No data available
              Antibodies
              No data available
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              GFPEFGGFP
              mRFP1EFGmRFP1
              1 - 2 of 2
              Show
              Mapping
              No data available
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              Citation
              Saralahti, A.K., Harjula, S.E., Rantapero, T., Uusi-Mäkelä, M.I.E., Kaasinen, M., Junno, M., Piippo, H., Nykter, M., Lohi, O., Rounioja, S., Parikka, M., Rämet, M. (2023) Characterization of the innate immune response to Streptococcus pneumoniae infection in zebrafish. PLoS Genetics. 19:e1010586e1010586.