Identification of genes related to resistance against S. Typhimurium in ovine macrophages
Mengyao Wang1, Dongbing Yang1, Zhexi Liu1
1Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China; National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China; Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China.
Abstract:
Salmonella enteric serovar Typhimurium (S. Typhimurium) is a zoonotic pathogen causing public health hazards. Identification of genes related to macrophages resistance to S. Typhimurium and their immune mechanisms can provide a theoretical basis for disease resistance. In this study, sixty significant differentially expressed genes were screened between susceptible and resistant sheep macrophages by transcriptome RNA-seq. Eight significantly enriched GO terms and six canonical pathways were involved by GO and KEGG enrichment analysis. Furthermore, knockdown of HMOX1 and SLPI increased remarkably the clearance of S. typhimurium, but SPP1 had little effect on the clearance of S. Typhimurium within sheep macrophages. Altogether, these results suggest that many genes of macrophages were reprogrammed via S. Typhimurium infection, some of which may facilitate host defence against Salmonella, while others allow Salmonella to escape.
Insights
This study identified genes in sheep macrophages that affect resistance to Salmonella Typhimurium (S. Typhimurium). Knocking down HMOX1 and SLPI genes enhanced bacterial clearance, offering insights into host defense mechanisms against Salmonella.
Area of Science:
- Immunology
- Genomics
- Microbiology
Background:
- Salmonella Typhimurium (S. Typhimurium) is a zoonotic pathogen posing significant public health risks.
- Understanding macrophage resistance mechanisms against S. Typhimurium is crucial for developing disease control strategies.
Purpose of the Study:
- To identify genes and immune mechanisms involved in sheep macrophage resistance to S. Typhimurium.
- To explore the role of specific genes in the host-pathogen interaction.
Main Methods:
- Transcriptome RNA sequencing (RNA-seq) was used to screen differentially expressed genes between susceptible and resistant sheep macrophages.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed.
- Gene knockdown experiments (HMOX1, SLPI, SPP1) were conducted to assess their effect on S. Typhimurium clearance.
Main Results:
- Sixty significantly differentially expressed genes were identified between susceptible and resistant macrophage populations.
- Eight GO terms and six KEGG pathways were significantly enriched, indicating key biological processes involved.
- Knockdown of HMOX1 and SLPI genes significantly increased S. Typhimurium clearance, while SPP1 showed minimal effect.
Conclusions:
- S. Typhimurium infection reprograms macrophage gene expression in sheep.
- Certain genes, such as HMOX1 and SLPI, play a role in facilitating host defense against Salmonella.
- Other genes may contribute to Salmonella's survival and evasion within macrophages.
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