Immune Modulation and the Development of Fowl Typhoid: A Model of Human Disease?

Abstract

Salmonella enterica serovar Gallinarum (S. Gallinarum) is the cause of typhoid in chickens but the immune factors that may facilitate the development of typhoid have not been fully elucidated. We show that, in contrast to non-typhoid S. Enteritidis infection, S. Gallinarum significantly reduced nitrite ion production and expression of mRNA for heterophil granulocyte chemoattractants CXCLi2 and IL-6 in chicken monocyte-derived macrophages (chMDMs) (p < 0.05) at 6 h post-infection (pi). S. Gallinarum also reduced IFN-γ and IL-17 expression by CD4+ lymphocytes cultured with infected chMDMs for 5 days but did not induce a Th2 phenotype or anergy. In vivo, S. Gallinarum also induced significantly lower expression of CXCLi1, CXCLi2, IL-1β, IL-6 and iNOS mRNA in the caecal tonsil by day 2 pi (p < 0.05–0.01) and consistently lower levels of IFN-γ, IL-18, IL-12, and IL-17. In the spleen, S. Gallinarum induced significantly lower levels of iNOS and IFN-γ (p < 0.01 and 0.05 respectively) and consistently lower levels of IL-18 and IL-12 but significantly greater (p < 0.01) expression of anti-inflammatory IL-10 at day 4 and 5 pi when compared to S. Enteritidis. This immune phenotype was associated with transit from the intestinal tissues to the liver by S. Gallinarum, not observed following S. Enteritidis infection. In conclusion, we report an immune mechanism that may facilitate typhoid disease in S. Gallinarum-infected chickens. However, down-regulation of inflammatory mediators, upregulation of IL-10, and associated liver colonisation are also characteristic of human typhoid, suggesting that this may also be a useful model of typhoid in humans.

Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?

“…Typhimurium were unable to do [ 187 ]. This immune phenotype is consistent to that reported by Tang et al [ 174 ] in chickens infected with S . Gallinarum, which also had a reduced expression of inflammatory mediators but increased levels of anti-inflammatory IL-10 production.…”

“…Pullorum have compared the host response to that induced by S. Enteritidis, a taxonomically closely related serovar which drives a strong inflammatory response in vivo and in vitro. This is characterised by high levels of IL-17, IL-12 and IL-18 in macrophages and IFNγ in CD4 + T lymphocytes co-cultured in vitro with infected macrophages [ 173 , 174 ]. In the spleen, S .…”

“…This immunomodulatory mechanism may facilitate typhoid disease in S . Gallinarum-infected chickens [ 174 ]. In comparison with S .…”

Nifuratel reduces Salmonella survival in macrophages by extracellular and intracellular antibacterial activity

“…One of the difficulties in treating the severe systemic diseases associated with typhoid and typhoid-like infections is the fact that Salmonella is essentially an intracellular pathogen, which means that antibiotic classes including aminoglycosides poorly penetrate the eukaryote cells and macrophages ( 17 , 18 ), which are the main cells involved as the host for multiplication of Salmonella during infections ( 19 , 20 ). In addition to the acute infection associated with extensive multiplication in organs rich in the macrophage-monocyte cell series, including the spleen and liver, acute infection involving the typhoid-producing serotypes may also be followed by persistent infection in a proportion of convalescents ( 21 ), with this probably depending on the genetic background of the host ( 22 ) and certainly on immune modulation by the pathogen ( 23 , 24 ).…”