Lipoteichoic acid from Staphylococcus aureus exacerbates respiratory disease in porcine respiratory coronavirus-infected pigs

Abstract

The objective of this study was to assess if lipoteichoic acid (LTA), produced by Staphylococcus aureus, exacerbates respiratory disease in porcine respiratory coronavirus (PRCV)-infected pigs, as has previously been shown with lipopolysaccharide. Piglets were inoculated with PRCV and 24h later with S. aureus LTA. Clinical signs, lung virus titres, inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were compared with those of animals in PRCV- and LTA-inoculated control groups. All PRCV-LTA-inoculated pigs except one developed severe respiratory disease, whereas clinical signs in the control groups were minimal or absent. Virus titres and grossly visible pulmonary lesions were similar in the PRCV-LTA- and PRCV-inoculated groups and were not detected in the LTA group. Neutrophil percentages in BALF were higher in the PRCV-LTA than in the PRCV group. There was no significant difference in interferon (IFN)-γ, interleukin (IL)-1, IL-6, IL-12/IL-23 and tumour necrosis factor (TNF)-α concentrations in BALF between the PRCV-LTA and PRCV groups, but levels of IL-6, IL-12/IL-23 and IFN-γ were higher in the PRCV-LTA-inoculated than in the LTA-inoculated controls. The findings suggest that the experimentally-induced respiratory disease was not mediated by cytokine over-production, but rather reflected the concerted action of particular cytokine interactions and/or as yet unidentified mediators. This is the first in vivo study to report the synergistic interaction between a virus and LTA in enhancing the severity of respiratory disease in the pig. Given that Gram-positive bacteria, capable of producing LTA, are commonly found in pig accommodation, the role of this compound in the development of the porcine respiratory disease complex requires further investigation.

Fig. 1

Development of mean clinical scores and the proportion of pigs exhibiting clinical signs in the group inoculated with both porcine respiratory coronavirus (PRCV) and lipoteichoic acid (LTA) (PRCV–LTA) (continuous line) compared to groups inoculated with either PRCV (long-dashed line) or LTA (short-dashed line). * One animal from each group was euthanased from this time onwards. The X axis signifies hours after inoculation with PRCV (before the slash) and LTA (after the slash).

Fig. 2

The concentrations of various cytokines in the bronchoalveolar lavage fluid of pigs in the porcine respiratory coronavirus (PRCV) and lipoteichoic acid (LTA)-inoculated group (PRCV–LTA) (triangles), and in groups given either PRCV (diamonds) or LTA (squares). The concentrations in the four sham-inoculated controls are represented as circles at time-point 0/0. The X axis signifies hours after inoculation with PRCV (before the slash) and LTA (after the slash).