Transcriptional Profiling of Hilar Nodes from Pigs after Experimental Infection with Actinobacillus Pleuropneumoniae

Abstract

The gram-negative bacterium Actinobacillus pleuropneumoniae (APP) is an inhabitant of the porcine upper respiratory tract and the causative agent of porcine pleuropneumonia (PP). In recent years, knowledge about the proinflammatory cytokine and chemokine gene expression that occurs in lung and lymph node of the APP-infected swine has been advanced. However, systematic gene expression profiles on hilar nodes from pigs after infection with Actinobacillus pleuropneumoniae have not yet been reported. The transcriptional responses were studied in hilar nodes (HN) from swine experimentally infected with APP and the control groupusing Agilent Porcine Genechip, including 43,603 probe sets. 9,517 transcripts were identified as differentially expressed (DE) at the p ≤ 0.01 level by comparing the log2 (normalized signal) of the two groups named treatment group (TG) and controls (CG). Eight hundred and fifteen of these DE transcripts were annotated as pig genes in the GenBank database (DB). Two hundred and seventy-two biological process categories (BP), 75 cellular components and 171 molecular functions were substantially altered in the TG compared to CG. Many BP were involved in host immune responses (i.e., signaling, signal transmission, signal transduction, response to stimulus, oxidation reduction, response to stress, immune system process, signaling pathway, immune response, cell surface receptor linked signaling pathway). Seven DE gene pathways (VEGF signaling pathway, Long-term potentiation, Ribosome, Asthma, Allograft rejection, Type I diabetes mellitus and Cardiac muscle contraction) and statistically significant associations with host responses were affected. Many cytokines (including NRAS, PI3K, MAPK14, CaM, HSP27, protein phosphatase 3, catalytic subunit and alpha isoform), mediating the proliferation and migration of endothelial cells and promoting survival and vascular permeability, were activated in TG, whilst many immunomodulatory cytokines were suppressed. The significant changes in the expression patterns of the genes, GO terms, and pathways, led to a decrease of antigenic peptides with antigen presenting cells presented to T lymphocytes via the major histocompatibility complex, and alleviated immune response induced APP of HN. The immune response ability of HN in the APP-infected pigs was weakened; however, cell proliferation and migration ability was enhanced.

Update onActinobacillus pleuropneumoniae-knowledge, gaps and challenges

“…Host transcriptional studies of App affected lungs (Brogaard et al., ; Cho, Jung, Kim, Ha, & Chae, ; Podolska et al., ; Zuo et al., ), lymph nodes (Yu et al., ) and liver (Skovgaard, Mortensen, Boye, Hedegaard, & Heegaard, ) identified several differentially expressed genes. Differential gene expression of these organs during App infection has also been demonstrated using cDNA microarrays (Hedegaard et al., ).…”

Concurrent host-pathogen gene expression in the lungs of pigs challenged with Actinobacillus pleuropneumoniae

“…The pathogenesis of pleuropneumonia in pigs is still not fully understood. However, innate pattern recognition receptors (PRRs) [ 13 ], inflammatory cytokines [ 14 , 15 ], and proteins involved in depletion of iron available to the bacteria [ 16 ] are recognized as important host factors associated with outcome of the infection. The rapidly evolving pleuropneumonia may in severe cases lead to death within 24–36 hours, likely due to the combined effect of tissue damage caused by the bacteria, and a strong proinflammatory immune response [ 15 , 17 ].…”

“…So far, studies of gene expression during porcine pleuropneumonia have addressed the pathogen or host separately [ 13 - 15 , 17 , 23 , 28 , 31 - 33 ]. Here, we analyzed the relationship between gene expression of A. pleuropneumoniae and the porcine host simultaneously in the same lung tissue samples.…”

The porcine innate immune system: An update

“…They are toxic for parasites but also host tissue. Transcriptional profiling of swine lung tissue and hilar lymph nodes after experimental infection with Actinobacillus pleuropneumoniae showed induction of many genes such as GM-CSF whose increased protein expression can stimulate stem cells to differentiate into granulocytes such as basophils, eosinophils and neutrophils (Yu et al, 2013;Zuo et al, 2013). miRNAs are evolutionarily conserved short single stranded RNAs that can inhibit gene expression at the post-transcriptional level playing an important role in the control of inflammation and immune response.…”