Host-pathogen interactions of Pasteurella multocida isolates of different origin were studied in a mouse model, focusing on pathology, bacterial load and expression of the metalloproteinase MMP9 and its inhibitor TIMP1. Intranasal inoculation with one of three doses (10(6), 10(4), 10(2) CFU) of an isolate from porcine pneumonia or fowl cholera showed marked differences between the two isolates. The avian isolate was highly pathogenic with severe signs of necrotizing pneumonia, liver necrosis and high bacterial load in lung and liver. Clinical signs and pathology related to the porcine isolate were dose dependent and consisted of exudative bronchopneumonia, abscess formation in liver and a lower bacterial load in lung and liver. Both isolates caused increased expression of MMP9 and TIMP1. In conclusion, evaluation and comparison of pathogenicity and host-pathogen interaction of P. multocida isolates from different hosts is possible in the intranasal murine model.