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Transcriptome analysis indicated that Salmonella lipopolysaccharide-induced thymocyte death and thymic atrophy were related to TLR4-FOS/JUN pathway in chicks.

ABSTRACT: Thymus is the crucial site for T cell development and once believed to be immune privileged. Recently, thymus has gained special attention as it is commonly targeted by infectious agents which may cause pathogenic tolerance and subsequent immunosuppression.We analyzed thymic responses to the challenge with Salmonella typhimurium (STm) or lipopolysaccharide (LPS) derived from STm in chicks. Newly hatched chicks were injected intraperitoneally with 5?×?10(4) CFU/mL STm or 50 mg/kg LPS. After LPS treatment, maximum thymocyte death (3?~?5-fold change) compared to controls was found at 12 h, and maximum loss of thymic weight (35 %) and reduced thymic index (20 %) were found at 36 h. After STm infection, maximum thymocyte death and thymic atrophy occurred at 36 and 72 h, respectively. No significant changes of thymic structure, chT1+ and CD4+/CD8+ T cell ratio were observed in thymus or spleen tissues after LPS treatment. Furthermore, transcriptome analysis revealed important roles for the TLR4-FOS/JUN signaling pathway in thymic injury. Thus, the major process of thymic atrophy in this study first involved activation of transcriptional factors FOS/JUN upon LPS binding to TLR4 that caused release of inflammatory factors, thereby inducing inflammatory responses and DNA damage and ultimately cell cycle arrest and thymic injury.STm and Salmonella LPS could induce acute chick thymic injury. LPS treatment acted faster than STm. TLR4-FOS/JUN pathway may play an important role in LPS induced chick thymic injury.

SUBMITTER: Huang H

PROVIDER: S-EPMC4855877 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Transcriptome analysis indicated that Salmonella lipopolysaccharide-induced thymocyte death and thymic atrophy were related to TLR4-FOS/JUN pathway in chicks.

Huang Haibo H Liu An A Wu Hui H Ansari Abdur Rahman AR Wang Jixiang J Huang Xiyao X Zhao Xing X Peng Kemei K Zhong Juming J Liu Huazhen H

BMC genomics 20160504

<h4>Background</h4>Thymus is the crucial site for T cell development and once believed to be immune privileged. Recently, thymus has gained special attention as it is commonly targeted by infectious agents which may cause pathogenic tolerance and subsequent immunosuppression.<h4>Results</h4>We analyzed thymic responses to the challenge with Salmonella typhimurium (STm) or lipopolysaccharide (LPS) derived from STm in chicks. Newly hatched chicks were injected intraperitoneally with 5 × 10(4) CFU/ ...[more]

PMID: 27142675

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Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of biological process. The goals of this study are to characterize the effects of genistein on the thymic transcriptome of chicks, when suffering from lipopolysaccharide challenge using RNA-Seq technology Methods: Thymic mRNA profiles of 21-day-old chicks with basic diet and lipopolysaccharide-treated, or lipopolysaccharide+genistein treated chick mice were generated by deep sequencing, in triplicate, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Results: Using an optimized data analysis workflow, we mapped about 70 million sequence reads per sample to the chicken genome and identified 25,016 transcripts with TopHat workflow. RNA-seq data confirmed stable expression of 25 known housekeeping genes, and 6 of these were validated with qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR for more than four orders of magnitude and a goodness of fit (R2) of 0.8798. We identified 712 DEGs (367 upregulated and 345 downregulated) between the LPS vs CON group with a |fold change| ＞1 (P ≤0.05, Figure 4 a). There are 1926 DEGs (1014 upregulated and 912 downregulated) in the GEN group compared with the LPS groupAltered expression of 6 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to retinal function. Conclusions: Our research has evidenced a novel finding in chicks that dietary genistein could inhibit the increased percentage of CD3+ T lymphocytes, and CD4+/CD8+ T lymphocyte ratio in the peripheral blood induced by lipopolysaccharide injection. Furthermore, dietary genistein exposure altered the mRNA expression profile and AS signatures in the thymus, and regulated the immune response, along with the improvement of thymus index and apoptotic index after lipopolysaccharide challenge. It would help to understand the role of dietary genistein to the regulation of immune function and provide theoretical support for improving healthy production of poultry.

Dataset Information

Transcriptome analysis indicated that Salmonella lipopolysaccharide-induced thymocyte death and thymic atrophy were related to TLR4-FOS/JUN pathway in chicks.

Publications

Transcriptome analysis indicated that Salmonella lipopolysaccharide-induced thymocyte death and thymic atrophy were related to TLR4-FOS/JUN pathway in chicks.

Similar Datasets

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