Tolerogenic Immunoregulation towards Salmonella Enteritidis Contributes to Colonization Persistence in Young Chicks

Long-term survival and the persistence of bacteria in the host suggest either host unresponsiveness or induction of an immunological tolerant response to the pathogen. The role of the host immunological response to persistent colonization of Salmonella Enteritidis (SE) in chickens remains poorly understood. In the current study, we performed a cecal tonsil transcriptome analysis in a model of SE persistent infection in 2-week-old chickens to comprehensively examine the dynamics of host immunological responses in the chicken gastrointestinal tract. Our results revealed overall host tolerogenic adaptive immune regulation in a major gut-associated lymphoid tissue, the cecal tonsil, during SE infection. Specifically, we observed consistent downregulation of the metallothionein 4 gene at all four postinfection time points (3, 7, 14, and 21 days postinfection [dpi]), which suggested potential pathogen-associated manipulation of the host zinc regulation as well as a possible immune modulatory effect. Furthermore, delayed activation in the B cell receptor signaling pathway and failure to sustain its active state during the lag phase of infection were further supported by an insignificant production of both intestinal and circulatory antibodies. Tug-of-war for interleukin 2 (IL-2) regulation between effector T cells and regulatory T cells appears to have consequences for upregulation in the transducer of ERBB2 (TOB) pathway, a negative regulator of T cell proliferation. In conclusion, this work highlights the overall host tolerogenic immune response that promotes persistent colonization by SE in young layer chicks.