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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Genome wide host gene expression analysis in mice experimentally infected with Pasteurella multocida
G Bhuvana Priya1, Viswas Konasagara Nagaleekar1, A Arun Prince Milton2
1Division of Bacteriology & Mycology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
Abstract:
Pasteurella multocida causes acute septicemic and respiratory diseases, including haemorrhagic septicaemia, in cattle and buffalo with case fatality of 100%. In the present study, mice were infected with P. multocida (1.6 × 103 cfu, intraperitoneal) to evaluate host gene expression profile at early and late stages of infection using high throughput microarray transcriptome analyses. Several differentially expressed genes (DEGs) at both the time points were identified in P.multocida infected spleen, liver and lungs. Functional annotation of these DEGs showed enrichment of key pathways such as TLR, NF-κB, MAPK, TNF, JAK-STAT and NOD like receptor signaling pathways. Several DEGs overlapped across different KEGG pathways indicating a crosstalk between them. The predicted protein-protein interaction among these DEGs suggested, that the recognition of P. multocida LPS or outer membrane components by TLR4 and CD14, results in intracellular signaling via MyD88, IRAKs and/or TRAF6 leading to activation of NFκB and MAPK pathways and associated cytokines.
Insights
This study reveals how the bacterium Pasteurella multocida triggers host immune responses in mice. Gene expression analysis identified key signaling pathways involved in the host
Area of Science:
- Veterinary Microbiology
- Immunology
- Genomics
Background:
- Pasteurella multocida causes fatal hemorrhagic septicemia in cattle and buffalo.
- Understanding host-pathogen interactions is crucial for disease control.
Purpose of the Study:
- To investigate host gene expression profiles during P. multocida infection in mice.
- To identify key immune signaling pathways activated by P. multocida.
Main Methods:
- Mice were infected with P. multocida.
- High-throughput microarray transcriptome analysis was performed on spleen, liver, and lung tissues.
- Differentially expressed genes (DEGs) were identified at early and late infection stages.
Main Results:
- Numerous DEGs were identified in infected organs.
- Enriched pathways included Toll-like receptor (TLR), NF-κB, MAPK, TNF, JAK-STAT, and NOD-like receptor signaling.
- Protein-protein interaction analysis suggested TLR4/CD14 recognition initiates signaling cascades via MyD88, IRAKs, and TRAF6, activating NF-κB and MAPK pathways.
Conclusions:
- P. multocida infection activates complex host immune signaling networks.
- TLR signaling plays a central role in recognizing P. multocida and initiating inflammatory responses.
- Identifying these pathways provides targets for potential therapeutic interventions.
