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- Title
Functional validation of the genetic architecture of Salmonella Enteritidis persistence in 129S6 mice.
- Authors
Chevenon, Marie; Naccache, Mayss; Eva, Megan; Khan, Rabia; Malo, Danielle
- Abstract
The Gram-negative bacteria, Salmonella, cause a broad spectrum of clinical diseases in humans, ranging from asymptomatic carriage to life-threatening sepsis. We have designed an experimental model to study the contribution of genetic factors to the persistence of Salmonella Enteritidis during the late phase of infection in 129S6/SvEvTac and C57BL/6J mice. C57BL/6J mice cleared the bacteria from their reticuloendothelial system within a period of 42 days, whereas the 129S6 mice still presented a high bacterial load. Using this model, we have identified ten Salmonella Enteritidis susceptibility loci ( Ses1, Ses1.1, and Ses3- Ses10) associated with bacterial persistence in target organs of 129S6/SvEvTac mice using a two-locus epistasis QTL linkage mapping approach. Significant statistical interactions were detected between Ses1 on chromosome 1 and Ses5 on chromosome 7 and between Ses1 and Ses4 on chromosome X. In this study, we functionally validated the genetic architecture of Salmonella persistence in 129S6 mice using single- (129S6.B6- Ses1.2 that combines Ses1 and Ses1.1 loci, 129S6.B6- Ses4, and 129S6.B6- Ses5) and double-congenic mice (129S6.B6- Ses1.2/ Ses4 and 129S6.B6- Ses1.2/ Ses5). These experiments demonstrate functional interactions between Ses1.2 and Ses4 or Ses5 that improve Salmonella Enteritidis clearance, validating the critical role played by gene-gene interactions in the contribution to bacterial clearance heritability. Improved bacterial clearance in double-congenic mice could be explained by the impact of Ses4 and Ses5 in combination with Ses1.2 on T polarization since a T2 bias (decreased Ifng and increased Il4 mRNA levels and reduced IgG2a immunoglobulins in the serum) was observed in 129S6.B6- Ses1.2/ Ses5 mice and a T17 (high Il17 expression) bias in 129S6.B6- Ses1.2/ Ses4.
- Subjects
SALMONELLA enterica; LABORATORY mice; GRAM-negative bacteria; BACTERIAL genetics; IMMUNOGLOBULINS; MESSENGER RNA
- Publication
Mammalian Genome, 2013, Vol 24, Issue 5/6, p218
- ISSN
0938-8990
- Publication type
Article
- DOI
10.1007/s00335-013-9453-3