Salmonella Pullorum effector SteE regulates Th1/Th2 cytokine expression by triggering the STAT3/SOCS3 pathway that suppresses NF-KB activation

Salmonella enterica serovar Pullorum (S. Pullorum) can regulate host immunity via special effectors that promote persistent infection and its intracellular survival. SteE as an anti-inflammatory effector is involved in the systemic infection of Salmonella in host macrophages. Macrophage activation can indirectly reflect the immune regulatory function of T helper type 1 (Th1)/T helper type 2 (Th2) cytokines. However, information concerning the regulation of Th1/Th2 cytokine expression by steE in S. Pullorum infection is limited. This study evaluates the effects of steE on the Th1/Th2 balance, STAT3/SOCS3 pathway, and NF-KB P65 activation in S. Pulloruminfected HD-11 cells and in chicken models. We demonstrated that steE diminished the expression of Th1related cytokines (IFN-& gamma; and IL-12) and promoted the expression of Th2-related cytokines (IL-4 and IL-10) in HD-11 cells and chicken models of S. Pullorum infection. SOCS3 silencing suppressed the function of steE in HD11 cells and led to the imbalance of Th1/Th2-related cytokines. SteE promoted SOCS3 expression by activating STAT3 in HD-11 cells. Moreover, steE inhibited NF-KB P65 expression and blocked its translocation to the nucleus by promoting SOCS3 expression. Our results illustrated that steE regulated the expression of Th1/Th2 cytokines via modulation of the STAT3/SOCS3 and NF-KB axis, which might be associated with Th1/Th2 cell differentiation and could, therefore, be a novel therapeutic strategy against salmonellosis.

Automated summary

Salmonella enterica serovar Pullorum can regulate host immunity via special effectors such as the anti-inflammatory effector SteE. It has been found that SteE can diminish the expression of Th1-related cytokines and promote the expression of Th2-related cytokines in both cells and chicken models infected with S. Pullorum. SteE achieves these effects by modulating the STAT3/SOCS3 and NF-KB pathways.