The invasion plasmid antigen J (IpaJ) from Salmonella inhibits the NF-κB activation by suppressing IκBα ubiquitination

Salmonella enterica serovar Pullorum (S. Pullorum) is the pathogen of pullorum disease, which leads to severe economic losses in many developing countries. In contrast to the strong inflammatory response induced by S. Typhimurium and S. Enteritidis, S. Pullorum causes systemic infection with little inflammation. The effector proteins secreted by Salmonella often play a crucial role in modulating host signal transduction and cellular processes to the pathogen9s advantage. In the present study, the IpaJ protein specifically identified in S. Pullorum was found to significantly inhibit activation of the key proinflammatory transcription factor, NF-κB, which was induced by TNFα, IL-1β, and LPS. IpaJ inhibited the NF-κB pathway in cells infected with S. Pullorum through the stabilization of IκBα. Deletion of ipaJ in S. Pullorum caused a significantly increased level of ubiquitinated IκBα and subsequently degraded by the proteasome in HeLa cells. Moreover, IpaJ was efficient in the prevention of NF-κB translocation to the nucleus and ultimately interfered with the secretion of the proinflammatory cytokines IL-1β, IL6, and IL8 in infected HeLa cells. Additionally, the transformation of ipaJ into S. Enteritidis decreased the secretion of proinflammatory cytokines in HeLa cells through suppression of the NF-κB pathway. The infection of chicken peripheral blood monocyte-derived macrophages (chMDM) confirmed that ipaJ-deleted S. Pullorum induced a stronger expression of proinflammatory cytokines than wild-type and complementary strains. In summary, the present study revealed that IpaJ functions as an important anti-inflammatory protein involved in S. Pullorum infection through inhibition of the NF-κB pathway and the subsequent inflammatory response.