Plasmin activity in the porcine airways is enhanced during experimental infection with Mycoplasma hyopneumoniae, is positively correlated with proinflammatory cytokine levels and is ameliorated by vaccination

Abstract

In Mycoplasma hyopneumoniae (Mhp) infection of swine, the host immune response is considered a major driver of lung pathology; however the underlying inflammatory mechanisms are not well understood. The serine protease plasmin is being increasingly recognised as a significant player in inflammatory processes. Here we compare plasmin activity in tracheobronchial lavage fluid (TBLF) from pigs experimentally challenged with Mhp that were either unvaccinated (n=10), or vaccinated with the commercial vaccine Suvaxyn(®) M.hyo (n=10). TBLF collected immediately prior to challenge and at 21 d and 35 d post-challenge was also assayed for levels of proinflammatory cytokines (TNF-α, IL-1β and IL-6), and for bacterial load (by qPCR). Clinical signs, pathology, cytokine analyses and qPCR all indicated that vaccinated pigs had significantly reduced disease relative to unvaccinated animals. Plasmin activity increased significantly in TBLF collected at 21 d post-challenge compared to pre-challenge TBLF in unvaccinated (P<0.01), but not vaccinated animals (P>0.05). A significant correlation was observed between bacterial load and plasmin activity in the 21 d (r=0.66; P<0.01) and the 35 d post-challenge samples, (r=0.62; P<0.01). Plasmin activity was also significantly correlated with levels of TNF-α, IL-1β and IL-6 at 21 d (r=0.78, P<0.0001; r=0.77, P<0.0001; r=0.64, P<0.005) and with TNF-α and IL-1β at 35 d post-challenge (r=0.77, P<0.0001; r=0.74, P<0.0005). Our results indicate that plasminogen is activated to plasmin in the respiratory tract of pigs as part of the host inflammatory response to Mhp infection and that this effect is ameliorated by vaccination.