A Model of Superinfection of Virus-Infected Zebrafish Larvae: Increased Susceptibility to Bacteria Associated With Neutrophil Death

Boucontet, L., Passoni, G., Thiry, V., Maggi, L., Herbomel, P., Levraud, J.P., Colucci-Guyon, E.
Frontiers in immunology   9: 1084 (Journal)
Registered Authors
Boucontet, Laurent, Herbomel, Philippe, Levraud, Jean-Pierre, Passoni, Gabriella
Shigella flexneri, Sindbis virus, co-infection, innate immune response, live imaging, neutrophils, zebrafish
MeSH Terms
  • Animals
  • Bacterial Load
  • Biomarkers
  • Cell Line
  • Cytokines/genetics
  • Cytokines/metabolism
  • Disease Models, Animal*
  • Disease Susceptibility*
  • Gene Expression
  • Larva
  • Leukocyte Count
  • Neutrophils/immunology*
  • Neutrophils/metabolism
  • Superinfection*
  • Viral Load
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish/microbiology*
  • Zebrafish/virology*
29881380 Full text @ Front Immunol
Enhanced susceptibility to bacterial infection in the days following an acute virus infection such as flu is a major clinical problem. Mouse models have provided major advances in understanding viral-bacterial superinfections, yet interactions of the anti-viral and anti-bacterial responses remain elusive. Here, we have exploited the transparency of zebrafish to study how viral infections can pave the way for bacterial co-infections. We have set up a zebrafish model of sequential viral and bacterial infection, using sublethal doses of Sindbis virus and Shigella flexneri bacteria. This virus induces a strong type I interferons (IFN) response, while the bacterium induces a strong IL1β and TNFα-mediated inflammatory response. We found that virus-infected zebrafish larvae showed an increased susceptibility to bacterial infection. This resulted in the death with concomitant higher bacterial burden of the co-infected fish compared to the ones infected with bacteria only. By contrast, infecting with bacteria first and virus second did not lead to increased mortality or microbial burden. By high-resolution live imaging, we showed that neutrophil survival was impaired in Sindbis-then-Shigella co-infected fish. The two types of cytokine responses were strongly induced in co-infected fish. In addition to type I IFN, expression of the anti-inflammatory cytokine IL10 was induced by viral infection before bacterial superinfection. Collectively, these observations suggest the zebrafish larva as a useful animal model to address mechanisms underlying increased bacterial susceptibility upon viral infection.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes