Autoimmune-Disease-Prone NOD Mice Help To Reveal a New Genetic Locus for Reducing Pulmonary Disease Caused by Mycoplasma pulmonis

Abstract

Mycoplasmas are bacterial pathogens of a range of animals, including humans, and are a common cause of respiratory disease. However, the host genetic factors that affect resistance to infection or regulate the resulting pulmonary inflammation are not well defined. We and others have previously demonstrated that nonobese diabetic (NOD) mice can be used to investigate disease loci that affect bacterial infection and autoimmune diabetes. Here we show that NOD mice are more susceptible than C57BL/6 (B6) mice to infection with , a natural model of pulmonary mycoplasmosis. The lungs of infected NOD mice had higher loads of and more severe inflammatory lesions. Moreover, congenic NOD mice that harbored different B6-derived chromosomal intervals enabled identification and localization of a new mycoplasmosis locus, termed , on chromosome 13. These congenic NOD mice demonstrated that the B6 allele for reduced the severity of pulmonary inflammation caused by infection with and that this was associated with altered cytokine and chemokine concentrations in the infected lungs. also colocalizes to the same genomic interval as and, genetic loci linked to listeriosis resistance and autoimmune diabetes susceptibility, respectively, suggesting that allelic variation within these loci may affect the development of both infectious and autoimmune disease.

Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice

“…Phenotypic variations of host response to M. pulmonis infection have been demonstrated in several inbred mouse strains(4,5,46) and autoimmune disease mouse(54). In Chapter 1, it was shown that classical inbred strains of mice manifested an extreme response, highly resistant or highly susceptible to M. pulmonis infection.…”

Characterization of genetic humanized mice with transgenic HLA DP401 or DRA but deficient in endogenous murine MHC class II genes upon Staphylococcus aureus pneumonia

“…Entire lung sections stained with H&E were automatically digitized and analyzed using the TissueFAXS200 tissue slide analysis system (TissueGnostics, Austria). These images were further evaluated based on a histopathologic inflammatory scoring system as described previously, 27 which has been widely employed to analyze many mouse models of respiratory infections 28,29 …”

“…These images were further evaluated based on a histopathologic inflammatory scoring system as described previously, 27 which has been widely employed to analyze many mouse models of respiratory infections. 28 , 29 …”

“…These images were further evaluated based on a histopathologic inflammatory scoring system as described previously, 27 which has been widely employed to analyze many mouse models of respiratory infections. 28,29 Routine protocol for immunohistochemical analysis was used in this study, as previously described. 21 Frozen lung tissues were immediately placed in 10% neutral formaldehyde fixative for 12 h and cryoprotected in 30% sucrose in PBS at 4°C overnight; 10-to 12μm frozen sections were prepared using a cryostat.…”