Haemophilus parasuis induces activation of NF-κB and MAP kinase signaling pathways mediated by toll-like receptors

• H. parasuis infection induced the activation of p38/JNK MAPK pathway.
• H. parasuis infection activated NF-κB, p38 and JNK MAPK required for TLR1, TLR2, TLR4 and TLR6.
• H. parasuis infection-induced IL-8 and CCL4 expression were associated with both the NF-κB and p38/JNK MAPK pathways.
• MyD88/TRIF signaling cascades were essential for H. parasuis-induced NF-κB activation.

Glässer's disease in pigs caused by Haemophilus parasuis is characterized by a severe membrane inflammation. In our previous study, we have identified activation of the transcription factor NF-κB after H. parasuis infection of porcine epithelial cells. In this study, we found that H. parasuis infection also contributed to the activation of p38/JNK MAPK pathway predominantly linked to inflammation, but not the ERK MAPK pathway associated with growth, differentiation and development. Inhibition of NF-κB, p38 and JNK but not ERK activity significantly reduced IL-8 and CCL4 expression by H. parasuis. We also found TLR1, TLR2, TLR4 and TLR6 were required for NF-κB, p38 and JNK MAPK activation. Furthermore, MyD88 and TRIF signaling cascades were essential for H. parasuis-induced NF-κB activation. These results provided new insights into the molecular pathways underlying the inflammatory response induced by H. parasuis.