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

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.

Altered pathogenesis of porcine respiratory coronavirus in pigs due to immunosuppressive effects of dexamethasone: implications for corticosteroid use in treatment of severe acute respiratory syndrome coronavirus.

The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 10(7) PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2(+), CD3(+), CD4(+), and CD8(+) T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-gamma)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-gamma-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.