Porcine reproductive and respiratory syndrome virus infection increases CD14 expression and lipopolysaccharide-binding protein in the lungs of pigs

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is a respiratory virus of swine that plays an important role in multifactorial respiratory disease. European strains of PRRSV cause mild or no respiratory signs on their own, but can sensitize the lungs for the production of proinflammatory cytokines and respiratory signs upon exposure to bacterial lipopolysaccharides (LPS). The inflammatory effect of LPS depends on the binding to the LPS receptor complex. Therefore, we quantified the levels of CD14 expression and LPS-binding protein (LBP) in the lungs of pigs throughout a PRRSV infection. Twenty-four gnotobiotic pigs were inoculated intranasally with PRRSV (10(6) 50% tissue culture infectious doses per pig, Lelystad strain) or phosphate-buffered saline (PBS), and euthanized 1-52 days later. Lungs were examined for CD14 expression (immunofluorescence and image analysis), LBP (ELISA), and virus replication. PRRSV infection caused a clear increase of CD14 expression from 3 to 40 days post-inoculation (DPI) and LBP from 7 to 14 DPI. Both parameters peaked at 9-10 DPI (40 and 14 times higher than PBS control pigs, respectively) and were correlated tightly with virus replication in the lungs. Double immunofluorescence labelings demonstrated that resident macrophages expressed little CD14 and that the increase of CD14 expression in the PRRSV-infected lungs was probably due to infiltration of highly CD14-positive monocytes in the interstitium. As both CD14 and LBP potentiate the inflammatory effects of LPS, their increase in the lungs could explain why PRRSV sensitizes the lungs for the production of proinflammatory cytokines and respiratory signs upon exposure to LPS.