Gamma interferon influences intestinal epithelial hyperplasia caused by Lawsonia intracellularis infection in mice

Lawsonia intracellularis is a recently identified bacterial pathogen which causes disease in a broad range of animals. Invasion of intestinal epitheli al cells and the resultant hyperplasia of infected cells are central proces ses in disease pathogenesis. In this study, we aimed to establish whether i mmunocompetent mice were susceptible to infection and whether gamma interfe ron (IFN-gamma) contributed to the pathogenesis of infection. Wild-type 129 -Sv-Ev mice (129 mice) and IFN-gamma receptor knockout mice based on the 12 9 background (IFN-gammaR(-)) were challenged orally with approximately 5.5 x 10(7) L. intracellularis cells. Both 129 and IFN-gammaR(-) mice became in fected, although the extent of infection (as determined by the proportion o f infected crypts) was substantially lower in 129 mice than in IFN-gammaR(- ) mice. Despite these differences, infected crypts showed characteristics t ypical of proliferative enteropathies of other animals, i.e., intracellular colonization of epithelial cells by L. intracellularis with resultant epit helial hyperplasia. Infection in 129 mice was cleared between days 21 and 2 8 postchallenge, whereas infection in IFN-gammaR(-) mice was evident in 100 % of animals from day 21 onward. Additionally, in IFN-gammaR(-) mice the in fection was so extensive that fatalities resulted. IFN-gamma therefore play s a significant role in limiting intracellular infection and increased cell ular proliferation associated with L. intracellularis. L. intracellularis i nfection is generally associated with modest cellular infiltration; therefo re, further comparative examinations will be necessary to determine pathoge nicity factors and define the role of IFN-gamma in controlling this infecti on.