In vivo Inflammation of porcine lung induced by Gram-negative and Gram-positive bacterial components

Pathogen associated molecular patterns (PAMPs) are conserved molecules of microorganisms that has been implicated as an important factor in the inflammatory response following bacterial infection. We studied the effects of two different PAMPs [lipoteichoic acid (LTA) and lipopolysaccharide (LPS)] relevant for respiratory infections in lung inflammation, as well as to compare their combined effect in pigs. For this purpose, post-weaned piglets were inoculated intranasally with LPS, LTA, LPS plus LTA, or control for 24 hours period. Clinical signs, lung lesions, inflammatory cells in bronchoalveolar lavage fluid (BALF) were assessed. In addition, pro-inflammatory cytokine profiles and myeloperoxidase (MPO) release by inflammatory cells were measured. Co-inoculated group animals showed minimal respiratory signs. Grossly visible pulmonary lesions were similar in LPS and LPS plus LTA inoculated groups. Clinical signs and gross pulmonary lesions were not detected in LTA group. Neutrophil percentages in BALF were significantly higher in combined inoculated group than LPS or LTA alone. LPS and LTA plus LPS treated animals released TNF-α, IL-1β and IL-8, while LTA had no effect except releasing only low concentration of IL-8. Combined inoculation produced significantly elevated levels of IL-8 and TNF-α when compared to LPS alone. Notably, low level of IL-6 was induced by LPS and combined inoculated group. Moreover, MPO level was significantly higher in co-treated group than LPS, but LTA had no effect. In general, marked differences were detected among PAMPs-induced lung inflammation. Overall, compared to LPS, LTA was a relatively weak inflammation inducer. This in vivo study may suggest the synergistic interaction between LPS and LTA in enhancing the severity of pulmonary inflammation, which may be of consequence for understanding pathogenic mechanism at play during Gram-negative and Gram-positive respiratory tract infection.