Genetic control of the immune response in pathogenesis

Background: Epidemiological studies have suggested that there is a genetic component to susceptibility to chronic periodontitis. Studies in humans and in animal models have suggested that some of the important components may be polymorphisms in key immunological genes. Methods: This paper summarizes previously published data from a mouse model in which alveolar bone loss is induced by oral infection with Porphyromonas gingivalis. Mice of different inbred immune-normal strains were used, as well as the F1 heterozygotes from crosses between strains. In addition, tissue expression of an array of immunological genes was measured in the gingiva and spleen of these mice by quantitative reverse transcription-polymerase chain reaction (QPCR). Results: Not all strains of mice are susceptible to bone loss. Intercross experiments demonstrate that susceptibility is an inherited trait. A subset of immunological genes tested showed differential basal expression in the gingiva or spleens (or both). Tumor necrosis factor and osteoprotegerin mRNAs are more highly expressed in the gingiva and interleukin-1 mRNA is more highly expressed in both the gingiva and the spleens of susceptible mice than resistant mice. In the resistant mice, interleukin-15 mRNA in the gingiva and Selp mRNA in the spleen are present at higher levels. In the resistant mice no genes changed expression after P. gingivalis infection, while mRNA for interleukin-1, osteoprotegerin, and STAT6 all increased in the susceptible mice. Conclusions: Susceptibility and resistance are heritable traits. Strain differences in basal mRNA expression correlate with differences in susceptibility. Genes that change expression in response to infection also correlate with differences in susceptibility.