Abstract
Indiscriminate use of antibiotics to treat infections that are of viral origin contributes to unnecessary use which potentially may induce resistance in commensal bacteria. To counteract this a number of host gene transcriptional studies have been conducted to identify genes that are differently expressed during bacterial and viral infections in humans, and thus could be used as a tool to base decisions on the use of antibiotics. In this paper, we aimed to evaluate the potential of a selection of genes that have been considered biomarkers in humans, to differentially diagnose bacterial from viral infections in the pig. First porcine PBMC were induced with six toll-like receptor (TLR) agonists (FliC, LPS, ODN 2216, Pam3CSK4, poly I:C, R848) to mimic host gene expression induced by bacterial or viral pathogens, or exposed to heat-killed Actinobacillus pleuropneumoniae or a split influenza virus. Genes that were differentially expressed between bacterial and viral inducers were further evaluated on clinical material comprising eleven healthy pigs, and six pigs infected with A. pleuropneumoniae. This comprised three virally upregulated genes (IFI44L, MxA, RSAD2) and four bacterially upregulated genes (IL-1β, IL-8, FAM89A, S100PBP). All six infected pigs could be differentially diagnosed to healthy pigs using a host gene transcription assay based on the geometric average of the bacterially induced genes IL-8 and S100PBP over that of the virally induced gene MxA.
Highlights
Antimicrobial resistance is a globally emerging problem, threatening human and animal health [1]
We have previously evaluated acute-phase proteins and pro-inflammatory cytokines in studies of the efficacy of various antibiotics during experimental infections with the respiratory pathogen Actinobacillus pleuropneumoniae causing severe disease [13,14,15] and serum IFN-α as an indicator for ongoing viral infections [16,17,18]
Porcine Peripheral blood mononuclear cells (PBMC) exposed to six different toll-like receptor (TLR) agonists were screened for the expression of putative marker genes for bacterial or viral infections as well as genes indicative of TLR activation (Table 2)
Summary
Antimicrobial resistance is a globally emerging problem, threatening human and animal health [1]. The amount of antimicrobials used in the livestock sector exceeds that in the health sector and most of these antimicrobials are used in intensive pig rearing [2]. The latter is attributable to the practice of using antibiotics regularly for disease prevention and for promoting growth. A transcript signature differentiating bacterial from viral infections in pigs salaries). BH, CL, ES and UM received parts of their salaries from this fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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