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

Shin MK, Park H, Shin SW, Jung M, Lee SH, Kim DY, Yoo HS - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

No MeSH data available.


Related in: MedlinePlus

Representative network of the genes with altered expression in MAP-challenged mice at 3 and 6 weeks p.i.Two networks showing common genes and functions at 3 and 6 weeks p.i. were merged. The purple line indicates overlapped genes and relationships between 3 and 6 weeks p.i. Individual nodes represent proteins, with relationships represented by edges. Nodes are colored to indicate changes in gene expression, with red indicating up-regulation, green indicating down-regulation, and white indicating that the gene/factor was not differentially expressed. Solid lines indicate a direct interaction and dotted lines indicate an indirect interaction. Arrows indicate directional relationships.
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pone.0138770.g005: Representative network of the genes with altered expression in MAP-challenged mice at 3 and 6 weeks p.i.Two networks showing common genes and functions at 3 and 6 weeks p.i. were merged. The purple line indicates overlapped genes and relationships between 3 and 6 weeks p.i. Individual nodes represent proteins, with relationships represented by edges. Nodes are colored to indicate changes in gene expression, with red indicating up-regulation, green indicating down-regulation, and white indicating that the gene/factor was not differentially expressed. Solid lines indicate a direct interaction and dotted lines indicate an indirect interaction. Arrows indicate directional relationships.

Mentions: Two networks that showed common genes and functions between 3 and 6 weeks p.i., were merged to investigate the relationships among the differentially expressed genes. The representative network of the differentially expressed genes at 3 and 6 weeks p.i. showed enrichment for factors associated with endocrine system disorders, gastrointestinal disease, immunological diseases, developmental disorders, and hereditary disorders (Fig 5). This network contained IFN-γ (2.4- and 1.9-fold up-regulation at 3 and 6 weeks p.i., respectively) and genes encoding complement components including C1q (C1qa, 2.3- and 3.9-fold up-regulation; C1qb, 2.9- and 5.1-fold up-regulation; C1qc, 3.0- and 4.9-fold up-regulation at 3 and 6 weeks p.i., respectively); transmembrane receptors such as scavenger receptor class F, member 1 (Scarf1, 2.8- and 3.1-fold up-regulation at 3 and 6 weeks p.i.); triggering receptor expressed on myeloid cells 3 (Trem3, 2.7- and 4.7-fold up-regulation at 3 and 6 weeks p.i., respectively); major histocompatibility complex class II molecules (Hla-dmb, 3.2- and 2.3-fold down-regulation; Hla-doa, 2.9- and 2.3-fold down-regulation; Hla-dob, 5.5- and 4.0-fold down-regulation at 3 and 6 weeks p.i., respectively); C-type lectin domain family 2, member D (Clec2d, 2.6- and 2.1-fold down-regulation at 3 and 6 weeks p.i., respectively); killer cell lectin-like receptor subfamily E, member 1 (Klre1, 2.9-fold down-regulation at 3 weeks p.i.); and guanylate binding proteins (Gbp5, 2.4- and 1.7-fold up-regulation; Gbp6, 3.7- and 2.6-fold up-regulation at 3 and 6 weeks p.i.).


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

Shin MK, Park H, Shin SW, Jung M, Lee SH, Kim DY, Yoo HS - PLoS ONE (2015)

Representative network of the genes with altered expression in MAP-challenged mice at 3 and 6 weeks p.i.Two networks showing common genes and functions at 3 and 6 weeks p.i. were merged. The purple line indicates overlapped genes and relationships between 3 and 6 weeks p.i. Individual nodes represent proteins, with relationships represented by edges. Nodes are colored to indicate changes in gene expression, with red indicating up-regulation, green indicating down-regulation, and white indicating that the gene/factor was not differentially expressed. Solid lines indicate a direct interaction and dotted lines indicate an indirect interaction. Arrows indicate directional relationships.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595071&req=5

pone.0138770.g005: Representative network of the genes with altered expression in MAP-challenged mice at 3 and 6 weeks p.i.Two networks showing common genes and functions at 3 and 6 weeks p.i. were merged. The purple line indicates overlapped genes and relationships between 3 and 6 weeks p.i. Individual nodes represent proteins, with relationships represented by edges. Nodes are colored to indicate changes in gene expression, with red indicating up-regulation, green indicating down-regulation, and white indicating that the gene/factor was not differentially expressed. Solid lines indicate a direct interaction and dotted lines indicate an indirect interaction. Arrows indicate directional relationships.
Mentions: Two networks that showed common genes and functions between 3 and 6 weeks p.i., were merged to investigate the relationships among the differentially expressed genes. The representative network of the differentially expressed genes at 3 and 6 weeks p.i. showed enrichment for factors associated with endocrine system disorders, gastrointestinal disease, immunological diseases, developmental disorders, and hereditary disorders (Fig 5). This network contained IFN-γ (2.4- and 1.9-fold up-regulation at 3 and 6 weeks p.i., respectively) and genes encoding complement components including C1q (C1qa, 2.3- and 3.9-fold up-regulation; C1qb, 2.9- and 5.1-fold up-regulation; C1qc, 3.0- and 4.9-fold up-regulation at 3 and 6 weeks p.i., respectively); transmembrane receptors such as scavenger receptor class F, member 1 (Scarf1, 2.8- and 3.1-fold up-regulation at 3 and 6 weeks p.i.); triggering receptor expressed on myeloid cells 3 (Trem3, 2.7- and 4.7-fold up-regulation at 3 and 6 weeks p.i., respectively); major histocompatibility complex class II molecules (Hla-dmb, 3.2- and 2.3-fold down-regulation; Hla-doa, 2.9- and 2.3-fold down-regulation; Hla-dob, 5.5- and 4.0-fold down-regulation at 3 and 6 weeks p.i., respectively); C-type lectin domain family 2, member D (Clec2d, 2.6- and 2.1-fold down-regulation at 3 and 6 weeks p.i., respectively); killer cell lectin-like receptor subfamily E, member 1 (Klre1, 2.9-fold down-regulation at 3 weeks p.i.); and guanylate binding proteins (Gbp5, 2.4- and 1.7-fold up-regulation; Gbp6, 3.7- and 2.6-fold up-regulation at 3 and 6 weeks p.i.).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

No MeSH data available.


Related in: MedlinePlus