Abstract
BackgroundThe complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Here, we infected specific pathogen-free Mus musculus with App serotype 7 by intranasal inoculation to construct an acute hemorrhagic pneumonia infection model and isolated the infected lungs for analysis of the interactions by dual RNA-seq.ResultsFour cDNA libraries were constructed, and 2428 differentially expressed genes (DEGs) of the host and 333 DEGs of App were detected. The host DEGs were mainly enriched in inflammatory signaling pathways, such as the TLR, NLR, RLR, BCR and TCR signaling pathways, resulting in large-scale cytokine up-regulation and thereby yielding a cytokine cascade for anti-infection and lung damage. The majority of the up-regulated cytokines are involved in the IL-23/IL-17 cytokine-regulated network, which is crucial for host defense against bacterial infection. The DEGs of App were mainly related to the transport and metabolism of energy and materials. Most of these genes are metabolic genes involved in anaerobic metabolism and important for challenging the host and adapting to the anaerobic stress conditions observed in acute hemorrhagic pneumonia. Some of these genes, such as adhE, dmsA, and aspA, might be potential virulence genes. In addition, the up-regulation of genes associated with peptidoglycan and urease synthesis and the restriction of major virulence genes might be immune evasion strategies of App. The regulation of metabolic genes and major virulence genes indicate that the dominant antigens might differ during the infection process and that vaccines based on these antigens might allow establishment of a precise and targeted immune response during the early phase of infection.ConclusionThrough an analysis of transcriptional data by dual RNA-seq, our study presents a novel global view of the interactions of App with its host and provides a basis for further study.
Highlights
The complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection
The infected lungs were isolated for dual RNA-seq, and the transcriptional differences of App and Mus musculus (Mmu) between infection and non-infection conditions were revealed
The identified host differentially expressed genes (DEGs) were mainly up-regulated and activated many immune signaling pathways, such as the Toll-like receptor (TLR), NOD-like receptor (NLR), RIG-I-like receptor (RLR), RIG-I, B cell receptor (BCR), and T cell receptor (TCR) signaling pathways, and caused upregulation of Csf2, Cxcl2, Il6, Ccl4, Il1b, Il23α, Il1α, Il10, Il17f, Il17a, Tnf, and Ifng, among other cytokines, leading to an anti-infection cytokine cascade and causing lung damage. Most of these cytokines are involved in the IL23/IL-17 cytokine interaction network, which might play a significant role for the host in App infection
Summary
The complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Actinobacillus pleuropneumonia (App) can cause serious porcine respiratory diseases with high incidence and mortality rates. Even with the optimization of intensive and large-scale breeding patterns and the development of vaccines for the disease, many districts have observed high morbidity rates due to App in recent years [2,3,4]. This disease is airborne, and the wild strains can break through the defense of a sound vaccine prevention and control system, resulting in rapid proliferation. Researchers have analyzed the function of these genes, such as HgbA [9], ureC [10] and apxIA [11], through gene knockout to construct gene deletion mutants, providing more choices for subunit vaccine production
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
