Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

Abstract

The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14-18 h after lung infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14-18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase protein response occurring concomitantly with the hepatic response. This suggests that the acute phase protein response is a more disseminated systemic response than previously thought. The current study provides to our knowledge the first example of porcine extrahepatic expression and regulation of C-reactive protein, haptoglobin, fibrinogen, pig major acute phase protein, and transferrin in peripheral lymphoid tissues.

Figure 1.

Analysis of gene expression changes of SAA2, Hp, CRP, IL-6, and PigMAP in different tissues in the group of infected animals (n = 10), compared to leukocyte expression values (set to 1). Standard error of the mean (SEM) is illustrated by error bars. Wilcoxon rank sum test was used to evaluate the significance of the tissue specific differences in gene expression compared to leukocytes. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 2.

Serum concentrations in individual pigs of SAA, CRP, Hp and TTR before (−1 dpi) and after (1 dpi) inoculation with A. pleuropneumoniae. White bars represent uninfected controls (Nos. 23 and 24), and grey bars represent samples from inoculated animals (Nos. 25–36, depicted in numerical order). Detection limits are indicated by horizontal, dotted lines. Protein concentrations were determined by ELISA as described in the text. Mean and SD of two determinations are shown except for TTR (single determinations).