Dataset Information

Gene expression profiling in the lungs of pigs with different susceptibilities to Glasser's disease.

ABSTRACT:

Background

Haemophilus parasuis is the causative agent of Glässer's disease in pigs. Currently, little is known about the molecular mechanisms that contribute to disease susceptibility. This study used a porcine oligonucleotide microarray to identify genes that were differentially expressed (DE) in the lungs of colostrum-deprived animals previously characterized as being either 'Fully Resistant' (FR) or 'Susceptible' to infection by H. parasuis in a bacterial challenge experiment.

Results

Gene expression profiles of 'FR' and 'Susceptible' animals were obtained by the identification of genes that were differentially expressed between each of these groups and mock-inoculated 'Control' animals. At 24 hours post-inoculation, a total of 21 and 58 DE genes were identified in 'FR' and 'Susceptible' animals respectively. At 72 hours, the numbers of genes were 20 and 347 respectively. 'FR' animals at 24 hours exhibited an increased expression of genes encoding extracellular matrix and TGF-beta signalling components, possibly indicative of tissue repair following the successful early resolution of infection. The gene expression profile of 'FR' animals at 72 hours supported the hypothesis that higher levels of antibacterial activity were responsible for the 'FR' phenotype, possibly due to an increase in natural immunoglobulin A and decrease in signalling by the immunoregulatory transcription factor peroxisome proliferator-activated receptor gamma (PPAR-gamma). The expression profile of 'Susceptible' animals at both time-points was characterized by an imbalance in signalling between pro and anti-inflammatory cytokines and an increased expression of genes involved in biological processes associated with inflammation. These include the pro-inflammatory cytokine genes resistin (RETN) and interleukin 1-beta (IL1B). At 72 hours, a reduction in the expression of genes involved in antigen presentation by both MHC class I and II molecules was observed, which could have contributed to the inability of 'Susceptible' animals to clear infection.

Conclusions

This study is the first to have identified discrete sets of DE genes in pigs of differing susceptibility to H. parasuis infection. Consequently, several candidate genes and pathways for disease resistance or susceptibility phenotypes have been identified. In addition, the findings have shed light on the molecular pathology associated with Glässer's disease.

SUBMITTER: Wilkinson JM

PROVIDER: S-EPMC3017779 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The local transcriptional response was studied in different locations of lungs from pigs experimentally infected with the respiratory pathogen Actinobacillus pleuropneumoniae serotype 5B, using porcine cDNA microarrays. This infection gives rise to well-demarcated infection loci in the lung, characterized by necrotic and haemorrhagic lesions. Lung tissue was sampled from necrotic areas, from visually unaffected areas and from areas bordering on necrotic areas. Expression pattern of these areas from infected pigs was compared to healthy lung tissue from un-infected pigs. Transcription of selected genes important in the innate defence response were further analysed by quantitative real-time reverse-transcriptase PCR. A clear correlation was observed between the number of differentially expressed genes as well as the magnitude of their induction and the sampling location in the infected lung, with the highest number of differentially expressed genes, and the most highly induced genes found in necrotic areas. Interestingly, a group of differentially regulated genes was represented in all three areas, comprising genes encoding cytokines, acute phase proteins, and factors related to regulation of apoptosis and the complement system. Interferon-gamma was down-regulated in both necrotic and bordering areas. Evidence of neutrophil recruitment was seen by the up-regulation of chemotactic factors for neutrophils. In conclusion, we found subsets of genes expressed at different levels in the three selected areas of the infected lung as compared to the control group. Thus it is demonstrated that an infection with clearly defined infected loci leads to a rapid disseminated intra-organ response in neighbouring seemingly unaffected tissue areas of the infected organ. Within the lung, we found a clear division of induced genes as, in unaffected areas a large part of differently expressed genes were involved in systemic reactions to infections, while differently expressed genes in necrotic areas were mainly concerned with homeostasis regulation.