Model of Persistent Salmonella Infection: Salmonella enterica Serovar Pullorum Modulates the Immune Response of the Chicken from a Th17-Type Response towards a Th2-Type Response

Salmonella enterica infection affects a wide range of animals and humans, and a small number of serovars cause typhoid-like infections, one characteristic of which is persistent infection in convalescents. Avian-specific S. enterica serovar Pullorum produces systemic disease in young chickens, which is followed by a carrier state in convalescent birds, leading to infection of the ovary at sexual maturity and vertical transmission. However, the immunological basis of persistent infection remains unclear. S. enterica serovar Enteritidis is taxonomically closely related but does not show this characteristic. Differences in the immune responses between S. Pullorum and S. Enteritidis were compared by using Salmonella-infected chicken monocyte-derived macrophages (chMDMs) and CD4(+) T lymphocytes that had been cocultured with infected chMDMs or chicken splenocytes in vitro and also in 2-dayold chickens in vivo. In comparison with S. Enteritidis, S. Pullorum-infected chMDMs showed reduced mRNA expression levels of interleukin-12 alpha (IL-12 alpha) and IL-18 and stimulated the proliferation of Th2 lymphocytes, with reduced expression of gamma interferon (IFN-gamma) and IL-17 and increased expression levels of IL-4 and IL-13. There was little evidence of clonal anergy or immune suppression induced by S. Pullorum in vitro. S. Pullorum also increased the levels of expression of IL-4 and decreased the levels of IFN-gamma in the spleen and cecal tonsil of infected birds. This suggests that S. Pullorum is able to modulate host immunity from a dominant IFN-gamma-producing Th17 response toward a Th2 response, which may promote persistent infection in chickens. S. Pullorum in chickens is presented as a good model of the typhoid group to study persistent infection.