Local and disseminated acute phase response during bacterial respiratory infection in pigs

The acute phase response is playing an important role, aiming to restore the healthy state after tissue injury, inflammation and infection. The biological function of this response and its interplay with other parts of innate defense reactions remain somewhat elusive. Expression of acute phase proteins (APP) outside the liver is increasingly recognized, still little is known of extra-hepatic production of APP in pigs. 14-18 h after experimental infection with Actinobacillus pleuropneumoniae, causing acute pleuropneumonia in pigs, we studied local APP gene expression changes in different locations of the infected lung (necrotic areas, areas bordering on necrotic areas, and from visually unaffected areas).

Expression differences was also studied in the liver and in peripheral lymphoid tissue (tracheobronchial lymph nodes, spleen, tonsils) of infected (n=10) and non-infected (n=5) pigs using reverse transcription quantitative real-time PCR (RT-qPCR). SAA, CRP and IL-6 were further measured in serum samples before and after the infection using ELISA.

Expression of ALB, A1AG, APOA1, CRP, Hp, PigMAP, SAA, TF, and TTR were found in all tissues investigated. SAA, Hp, LTF, LBP, TRF, SpA, SpD, IL-1α and IL-6 were found to be differentially expressed in all three areas of the infected lung compared to lung tissue from control pigs. Expression differences were general highest in necrotic areas.

We found good correlation between ELISA and RT-qPCR data the in serum and whole blood respectively. mRNA coding for CRP, Hp, IL-6, and SAA were found to be significantly up regulated in infected pigs in whole blood and tracheobronchial lymph nodes. In the spleen we found mRNA coding for APOA1, FIB, Hp, PigMAP, SAA, TF, and IL-6 to be differentially expressed.

In the tonsils IL-6 and SAA were also found differentially expressed between infected and control animals. We demonstrated that acute pleuropneumonia caused by A. pleuropneumoniae leads to a rapid disseminated local intra-lung APP response, also in apparently unaffected areas of the infected lung. Further extrahepatic expression of several acute-phase proteins was found 14-18h after experimental infection with A. pleuropneumoniae.

This firmly establishes that expression of APPs is widely disseminated, involving changes in the expression of APPs at a dynamic scale comparable to the hepatic response. These results suggest that many different cell-types in the organism are involved in production of APP and further supports that extrahepatic APP might be important players of the innate defence system.