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Epigenetic modification of TLRs in leukocytes is associated with increased susceptibility to Salmonella enteritidis in chickens.

Gou Z, Liu R, Zhao G, Zheng M, Li P, Wang H, Zhu Y, Chen J, Wen J - PLoS ONE (2012)

Bottom Line: Contrasting with the reduced expression of TLR genes, those of the zinc finger protein 493 (ZNF493) gene and Toll-interacting protein (TOLLIP) gene were enhanced in the susceptible chickens.Finally, the expression of TLR4 in peripheral blood mononuclear cells (PBMCs) infected in vitro with S. enteritidis increased significantly as a result of treatment with 5-Aza-2-deoxycytidine (5-Aza-dc) while either 5-Aza-dc or trichostatin A was effective in up-regulating the expression of TLR21 and TLR2-1.DNA methylation, in the predicted promoter region of TLR4 and TLR21 genes, and an exonic CpG island of the TLR2-1 gene was significantly higher in the susceptible chickens than in resistant chickens.

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Haidian, Beijing, China.

ABSTRACT
Toll-like receptors (TLRs) signaling pathways are the first lines in defense against Salmonella enteritidis (S. enteritidis) infection but the molecular mechanism underlying susceptibility to S. enteritidis infection in chicken remains unclear. SPF chickens injected with S. enteritidis were partitioned into two groups, one consisted of those from Salmonella-susceptible chickens (died within 5 d after injection, n = 6), the other consisted of six Salmonella-resistant chickens that survived for 15 d after injection. The present study shows that the bacterial load in susceptible chickens was significantly higher than that in resistant chickens and TLR4, TLR2-1 and TLR21 expression was strongly diminished in the leukocytes of susceptible chickens compared with those of resistant chickens. The induction of expression of pro-inflammatory cytokine genes, IL-6 and IFN-β, was greatly enhanced in the resistant but not in susceptible chickens. Contrasting with the reduced expression of TLR genes, those of the zinc finger protein 493 (ZNF493) gene and Toll-interacting protein (TOLLIP) gene were enhanced in the susceptible chickens. Finally, the expression of TLR4 in peripheral blood mononuclear cells (PBMCs) infected in vitro with S. enteritidis increased significantly as a result of treatment with 5-Aza-2-deoxycytidine (5-Aza-dc) while either 5-Aza-dc or trichostatin A was effective in up-regulating the expression of TLR21 and TLR2-1. DNA methylation, in the predicted promoter region of TLR4 and TLR21 genes, and an exonic CpG island of the TLR2-1 gene was significantly higher in the susceptible chickens than in resistant chickens. Taken together, the results demonstrate that ZNF493-related epigenetic modification in leukocytes probably accounts for increased susceptibility to S. enteritidis in chickens by diminishing the expression and response of TLR4, TLR21 and TLR2-1.

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Partially diminished inflammatory response in susceptible chickens.The relative expression of IL-6, IFN-β, TNF-α and IL-8 in susceptible (open bars) and resistant (filled bars) chickens at 8 h and 16 h after infection with S.enteritidis is shown. Data are means (n = 6), normalized to β-actin mRNA and the average expression at 0 h (**P<0.01). The vertical bar is the SD from the error mean square of the ANOVA. HPI is hours post-infection.
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pone-0033627-g002: Partially diminished inflammatory response in susceptible chickens.The relative expression of IL-6, IFN-β, TNF-α and IL-8 in susceptible (open bars) and resistant (filled bars) chickens at 8 h and 16 h after infection with S.enteritidis is shown. Data are means (n = 6), normalized to β-actin mRNA and the average expression at 0 h (**P<0.01). The vertical bar is the SD from the error mean square of the ANOVA. HPI is hours post-infection.

Mentions: Four pro-inflammatory cytokine genes (IL-6, IFN-β, TNF-α, and IL-8) were used to investigate if the decreased expression of TLR4, TLR21 and TLR2-1 at 16 h in susceptible chickens resulted in a mitigated inflammatory response. Consistent with the expression of TLRs in the resistant and susceptible groups, the induction of IL-6 and IFN-β transcription was greatly enhanced in the resistant, but not in the susceptible chickens at 16 h post-infection (Fig. 2). These results indicate that diminished expression of TLR4, TLR21 and TLR2-1 in the susceptible chickens leads to a decreased inflammatory response. The similar levels of IL-8 in both groups demonstrated that only some of the pro-inflammatory cytokines showed down-regulation in susceptible chickens, perhaps because IL-8 was regulated by other TLRs. In contrast, there was no obvious difference in the expression of TNF-α at 16 h, indicating that not all pro-inflammatory cytokine genes are induced at this early stage of infection (Fig. 2). Collectively, the results were consistent with higher susceptibility to S. enteritidis in birds being due to the partially diminished inflammatory response associated with decreased expression of TLR4, TLR21 and TLR2-1.


Epigenetic modification of TLRs in leukocytes is associated with increased susceptibility to Salmonella enteritidis in chickens.

Gou Z, Liu R, Zhao G, Zheng M, Li P, Wang H, Zhu Y, Chen J, Wen J - PLoS ONE (2012)

Partially diminished inflammatory response in susceptible chickens.The relative expression of IL-6, IFN-β, TNF-α and IL-8 in susceptible (open bars) and resistant (filled bars) chickens at 8 h and 16 h after infection with S.enteritidis is shown. Data are means (n = 6), normalized to β-actin mRNA and the average expression at 0 h (**P<0.01). The vertical bar is the SD from the error mean square of the ANOVA. HPI is hours post-infection.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3306431&req=5

pone-0033627-g002: Partially diminished inflammatory response in susceptible chickens.The relative expression of IL-6, IFN-β, TNF-α and IL-8 in susceptible (open bars) and resistant (filled bars) chickens at 8 h and 16 h after infection with S.enteritidis is shown. Data are means (n = 6), normalized to β-actin mRNA and the average expression at 0 h (**P<0.01). The vertical bar is the SD from the error mean square of the ANOVA. HPI is hours post-infection.
Mentions: Four pro-inflammatory cytokine genes (IL-6, IFN-β, TNF-α, and IL-8) were used to investigate if the decreased expression of TLR4, TLR21 and TLR2-1 at 16 h in susceptible chickens resulted in a mitigated inflammatory response. Consistent with the expression of TLRs in the resistant and susceptible groups, the induction of IL-6 and IFN-β transcription was greatly enhanced in the resistant, but not in the susceptible chickens at 16 h post-infection (Fig. 2). These results indicate that diminished expression of TLR4, TLR21 and TLR2-1 in the susceptible chickens leads to a decreased inflammatory response. The similar levels of IL-8 in both groups demonstrated that only some of the pro-inflammatory cytokines showed down-regulation in susceptible chickens, perhaps because IL-8 was regulated by other TLRs. In contrast, there was no obvious difference in the expression of TNF-α at 16 h, indicating that not all pro-inflammatory cytokine genes are induced at this early stage of infection (Fig. 2). Collectively, the results were consistent with higher susceptibility to S. enteritidis in birds being due to the partially diminished inflammatory response associated with decreased expression of TLR4, TLR21 and TLR2-1.

Bottom Line: Contrasting with the reduced expression of TLR genes, those of the zinc finger protein 493 (ZNF493) gene and Toll-interacting protein (TOLLIP) gene were enhanced in the susceptible chickens.Finally, the expression of TLR4 in peripheral blood mononuclear cells (PBMCs) infected in vitro with S. enteritidis increased significantly as a result of treatment with 5-Aza-2-deoxycytidine (5-Aza-dc) while either 5-Aza-dc or trichostatin A was effective in up-regulating the expression of TLR21 and TLR2-1.DNA methylation, in the predicted promoter region of TLR4 and TLR21 genes, and an exonic CpG island of the TLR2-1 gene was significantly higher in the susceptible chickens than in resistant chickens.

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Haidian, Beijing, China.

ABSTRACT
Toll-like receptors (TLRs) signaling pathways are the first lines in defense against Salmonella enteritidis (S. enteritidis) infection but the molecular mechanism underlying susceptibility to S. enteritidis infection in chicken remains unclear. SPF chickens injected with S. enteritidis were partitioned into two groups, one consisted of those from Salmonella-susceptible chickens (died within 5 d after injection, n = 6), the other consisted of six Salmonella-resistant chickens that survived for 15 d after injection. The present study shows that the bacterial load in susceptible chickens was significantly higher than that in resistant chickens and TLR4, TLR2-1 and TLR21 expression was strongly diminished in the leukocytes of susceptible chickens compared with those of resistant chickens. The induction of expression of pro-inflammatory cytokine genes, IL-6 and IFN-β, was greatly enhanced in the resistant but not in susceptible chickens. Contrasting with the reduced expression of TLR genes, those of the zinc finger protein 493 (ZNF493) gene and Toll-interacting protein (TOLLIP) gene were enhanced in the susceptible chickens. Finally, the expression of TLR4 in peripheral blood mononuclear cells (PBMCs) infected in vitro with S. enteritidis increased significantly as a result of treatment with 5-Aza-2-deoxycytidine (5-Aza-dc) while either 5-Aza-dc or trichostatin A was effective in up-regulating the expression of TLR21 and TLR2-1. DNA methylation, in the predicted promoter region of TLR4 and TLR21 genes, and an exonic CpG island of the TLR2-1 gene was significantly higher in the susceptible chickens than in resistant chickens. Taken together, the results demonstrate that ZNF493-related epigenetic modification in leukocytes probably accounts for increased susceptibility to S. enteritidis in chickens by diminishing the expression and response of TLR4, TLR21 and TLR2-1.

Show MeSH
Related in: MedlinePlus