Salmonella enterica infection affects a wide range of animals including humans. The avian specific serotype S. Pullorum infection produces systemic disease followed by a persistent carrier state in convalescence birds. Vaccination and other control strategies require an improved understanding of the immunity in response to S. Pullorum infection. This study compared the different immune dynamics following infection with (persistent) S. Pullorum and related (non-persistent) serovars S. Enteritidis and S. Gallinarum using co-culture of Salmonella-infected macrophages and CD4+ T lymphocytes in vitro and 2-day-old chickens in vivo. In comparison with S. Enteritidis, macrophages infected with S. Pullorum had a reduced gene expression of pro-inflammatory cytokines CXCLi2, IL-6, iNOS, IFN-γ, IL-12α and IL-18 and lower level of nitrite production. S. Pullorum-infected macrophages were found to be less effective than S. Enteritidis in stimulating the CD4+ lymphocytes to proliferate in vitro. CD4+ lymphocytes in co-culture with Salmonella-infected macrophages also produced lower levels of IFN-γ and IL-17F mRNA in response to S. Pullorum compared with S. Enteritidis. S. Pullorum infection in 2-day-old chickens stimulated proliferation of Th2-like lymphocytes with reduced IFN-γ and IL-17F but increased IL-4, IL-13 and IL-10 in the caecal tonsils and spleens when compared to S. Enteritidis. However, the modulation by S. Pullorum is not likely to be related to its large virulence plasmid, although the virulence plasmid of S. Gallinarum was shown to reduce nitrite production and gene expression of IL-1β and iNOS in infected HD11 cells. Our data showed no evidence of clonal anergy or immune suppression induced by S. Pullorum in vitro. The experimental work thus shows that the response to S. Pullorum infection was characterised by a modulation on host immunity from a dominant IFN-γ-producing Th17 response towards a Th2-like response which may promote persistent infection in chickens. This study provides insights into mechanisms by which S. Pullorum evades host immunity and produces the persistent carrier state. This opens the possibility for therapeutic application of cytokines to restore the host protective immune response to eliminate infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:689966 |
| Date | January 2016 |
| Creators | Tang, Ying |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/33663/ |
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