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

Abstract

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-κB P65 activation in S. Pullorum-infected HD-11 cells and in chicken models. We demonstrated that steE diminished the expression of Th1-related cytokines (IFN-γ 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 HD-11 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-κB 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-κB axis, which might be associated with Th1/Th2 cell differentiation and could, therefore, be a novel therapeutic strategy against salmonellosis.

• Authors: Zhike Liu, Li Wang, Pei Gao, Yan Yu, Yanhong Zhang, Anatoliy Fotin, Qiuxia Wang, Zhiyong Xu, Xiaobing Wei, Tetiana Fotina, Jinyou Ma
• Journal: Veterinary microbiology (Vet Microbiol) Vol. 284 Pg. 109817 (Sep 2023) ISSN: 1873-2542 [Electronic] Netherlands
• PMID: 37348209 (Publication Type: Journal Article)
• Copyright: Copyright © 2023. Published by Elsevier B.V.

Chemical References

• Cytokines
• NF-kappa B
• Suppressor of Cytokine Signaling Proteins

Topics

• Animals
• Cytokines (genetics)
• NF-kappa B (genetics)
• Signal Transduction
• Salmonella
• Suppressor of Cytokine Signaling Proteins
• Th1 Cells