Host Transcriptional Profiles and Immunopathologic Response following Mycobacterium avium subsp. paratuberculosis Infection in Mice

Abstract

Paratuberculosis or Johne’s disease is a chronic granulomatous enteropathy in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection. In the present study, we examined the host response to MAP infection in spleens of mice in order to investigate the host immunopathology accompanying host-pathogen interaction. Transcriptional profiles of the MAP-infected mice at 3 and 6 weeks p.i. showed severe histopathological changes, whereas those at 12 weeks p.i. displayed reduced lesion severity in the spleen and liver. MAP-infected mice at 3 and 6 weeks p.i. showed up-regulation of interferon-related genes, scavenger receptor, and complement components, suggesting an initial innate immune reaction, such as macrophage activation, bactericidal activity, and macrophage invasion of MAP. Concurrently, MAP-infected mice at 3 and 6 weeks p.i. were also suggested to express M2 macrophage phenotype with up-regulation of Mrc1, and Marco and down-regulation of MHC class II, Ccr7, and Irf5, and canonical pathways related to the T cell response including ICOS-ICOSL signaling in T helper cells, calcium-induced T lymphocyte apoptosis, and CD28 signaling in T helper cell. These results provide information which furthers the understanding of the immunopathologic response to MAP infection in mice, thereby providing insights valuable for research into the pathogenesis for MAP infection.

Potential biomarkers as an indicator of vertical transmission of Johne's disease in a Korean native cattle farm

“…In this study, gene expression profiles of biomarkers that were differentially expressed in MAP-infected animals in previous studies [ 5 24 28 29 ] were analyzed. Three genes ( S100A9 , LTF , and TIMP1 ) were significantly down-regulated in the calf group and one gene ( KLRB1 ) was significantly up-regulated in the cow group.…”

“…Tissue DNA was then analyzed by performing IS 900 real-time PCR and ISMAP02 nested PCR. Histopathological examination and acid-fast staining were performed as previously described [ 28 ].…”

“…Seven genes identified as prognostic biomarkers for MAP infection in previous research [ 5 24 28 29 ] were selected for use in this study. From whole blood collected from the jugular vein, total RNA was extracted by using a FavorPrep Blood/Cultured Cell Total RNA Mini kit (Favorgen Biotech Corporation, Taiwan) as previously described [ 24 ].…”

“…In recent years, transcriptomics and proteomics have been used to analyze the expression of genes and proteins in attempts to identify biomarkers of early stage MAP infection [ 13 18 19 ]. In our previous microarray method-based studies of cells and animal models, several biomarkers for diagnosis of early stage of PTB were proposed [ 24 28 29 ].…”

Revealing pathway cross-talk related to diabetes mellitus by Monte Carlo Cross-Validation analysis

“…There is no inclusive information for CD28 signaling in T helper cell in DM. Fortunately, Shin et al [32] have provided information that CD28 signaling in T helper cells was reduced following Mycobacterium avium subsp. paratuberculosis infection.…”