Host Transcriptional Profiles and Immunopathologic Response following Mycobacterium avium subsp. paratuberculosis
Min-Kyoung Shin1, Hongtae Park2, Seung Won Shin2
1Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul, Korea; Department of Microbiology, Gyeonsang National University School of Medicine, Jinju, Korea.
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.
Insights
This study reveals how mice respond to Mycobacterium avium subsp. paratuberculosis (MAP) infection, identifying key immune reactions and macrophage phenotypes. Findings offer insights into the immunopathology of Johne
Area of Science:
- Immunology
- Microbiology
- Veterinary Pathology
Background:
- Paratuberculosis (Johne's disease) is a chronic enteropathy in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP).
- Understanding the host-pathogen interaction and immunopathology is crucial for developing control strategies.
Purpose of the Study:
- To investigate the host immune response and immunopathology to MAP infection in a mouse model.
- To analyze transcriptional profiles and histopathological changes at different time points post-infection.
Main Methods:
- Transcriptional profiling of spleen tissues from MAP-infected mice at 3, 6, and 12 weeks post-infection.
- Histopathological examination of spleen and liver tissues.
- Analysis of gene expression related to innate and adaptive immune responses.
Main Results:
- Severe histopathological changes observed at 3 and 6 weeks, with reduced severity at 12 weeks post-infection.
- Up-regulation of interferon-related genes, scavenger receptors, and complement components, indicating innate immune activation (macrophage activation, bactericidal activity).
- Evidence of M2 macrophage phenotype and alterations in T cell-related signaling pathways (ICOS-ICOSL, CD28).
Conclusions:
- The study elucidates the dynamic immunopathologic response to MAP infection in mice.
- Findings highlight the interplay between innate and adaptive immunity during MAP infection.
- Provides valuable insights into MAP pathogenesis and potential therapeutic targets.
