Abstract

BackgroundNetwork biology (systems biology) approaches are useful tools for elucidating the host infection processes that often accompany complex immune networks. Although many studies have recently focused on Haemophilus parasuis, a model of Gram-negative bacterium, little attention has been paid to the host's immune response to infection. In this article, we use network biology to investigate infection with Haemophilus parasuis in an in vivo pig model.ResultsBy targeting the spleen immunogenome, we established an expression signature indicative of H. parasuis infection using a PCA/GSEA combined method. We reconstructed the immune network and estimated the network topology parameters that characterize the immunogene expressions in response to H. parasuis infection. The results showed that the immune network of H. parasuis infection is compartmentalized (not globally linked). Statistical analysis revealed that the reconstructed network is scale-free but not small-world. Based on the quantitative topological prioritization, we inferred that the C1R-centered clique might play a vital role in responding to H. parasuis infection.ConclusionsHere, we provide the first report of reconstruction of the immune network in H. parasuis-infected porcine spleen. The distinguishing feature of our work is the focus on utilizing the immunogenome for a network biology-oriented analysis. Our findings complement and extend the frontiers of knowledge of host infection biology for H. parasuis and also provide a new clue for systems infection biology of Gram-negative bacilli in mammals.

Highlights

  • Network biology approaches are useful tools for elucidating the host infection processes that often accompany complex immune networks

  • By extracting immune pathways from Kyoto Encyclopedia of Genes and Genomes (KEGG) and reactome databases, a total of 1,999 transcripts from the 20,201 transcripts arrayed on the chip were targeted as immunogenes according to the pathway annotation results

  • Recently, many studies have focused on the H. parasuis, a model Gram-negative bacterium

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Summary

Introduction

Network biology (systems biology) approaches are useful tools for elucidating the host infection processes that often accompany complex immune networks. We use network biology to investigate infection with Haemophilus parasuis in an in vivo pig model. Systems biology investigations of the transcriptome of host immunogenome could provide a profound exploration of the molecular events occurring, for example, the three- or even four-dimensional relationships between genes during a response to pathogen infection. This would increase our understanding of host resistance/susceptibility genes, immune response mechanisms, and molecular basis of hostpathogen interactions [14,15]. The systems biology approaches can provide us with powerful tools for uncovering the molecular immune mechanisms that defend against H. parasuis infection

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