SteE Enhances the Virulence of Salmonella Pullorum in Chickens by Regulating the Inflammation Response

Abstract

Salmonella enterica serovar Pullorum (S. Pullorum) is a host-specific pathogen, which causes acute gastroenteritis with high mortality in poultry. However, the association between steE, encoded by type III secretion system 2, and Salmonella virulence is not well-understood. To elucidate the functions of steE in S. Pullorum, ΔsteE strain was constructed using the λ-Red recombination technology. Compared to that in the wild-type, the deletion of steE in S. Pullorum reduced bacterial invasion, proliferation, and late apoptosis in the infected HD-11 cells. In addition, we analyzed the mRNA expression levels of effector genes and cytokines by qRT-PCR. SteE was associated with the regulation of various effector genes and inflammatory cytokines in HD-11 cells during S. Pullorum infection. The wild-type effector steE promoted the expression of anti-inflammatory cytokines (IL-4 and IL-10) and reduced that of pro-inflammatory cytokines (IL-1β, IL-6, and IL-12) compared to that in the ΔsteE-infected HD-11 cells and chicken spleens. Results from the chicken infection model showed that the deletion of steE resulted in significantly decreased colonization and long-term survival of the bacteria and alleviated pathological lesions compared to those in the wild-type. Further, steE increased the virulence of S. Pullorum in chickens by regulating the expression of inflammatory cytokines. Our findings provide insights into the persistent infection and autoimmunity associated with steE in S. Pullorum.

Speaking the host language: how Salmonella effector proteins manipulate the host

“…In this way, SteE drives an anti-inflammatory response in infected cells, counteracting the pro-inflammatory role of TNF⍺ in the granuloma [259] and resulting in the polarization of macrophages to an M2-like anti-inflammatory state that provides a niche for immune evasion, survival and persistence of Salmonella Typhimurium [260]. A similar role for SteE in the long-term survival of bacteria was recently observed in S. Pullorum-infected chickens [261].…”

“…A similar role for SteE in the long-term survival of bacteria was recently observed in S . Pullorum-infected chickens [ 261 ].…”