Intestinal Strictures, Fibrous Adhesions and High Local Interleukin-10 Levels in Goats Infected Naturally with Mycobacterium avium subsp. paratuberculosis
“…Macroscopic lesions occurred as early as 3 mpi predominantly in JPPs that were firm and thickened by granulomatous infiltration and had ulcerated surfaces. Mucosal ulcerations have been described in cases of naturally infected goats with diffuse intestinal lesions 19,24 and after experimental infection of goats with a mycobacterium isolated from patients with Crohn's disease. 42 The ulcerations we observed were frequently accompanied by transmural inflammation, resulting in foci of circumscribed serositis along the small intestine.…”
Section: Discussionmentioning
confidence: 99%
“…These may be the sites of origin of the strictures described in naturally infected goats. 19 The serositis facilitated a precise collection of altered intestine.…”
Section: Discussionmentioning
confidence: 99%
“…20 Variable findings have been reported concerning the preferential sites of lesions in the intestine of goats with paratuberculosis. Several studies found the jejunum most severely affected, 19,20,36,41 whereas others noted the distal small intestine. 25,40 In our investigation, predominantly JPPs in the proximal and mid-jejunum and the ICVPP were altered in subclinical paratuberculosis.…”
The development of lesions after infection with Mycobacterium avium subsp paratuberculosis (MAP) was examined in an experimental infection model. Goat kids were orally inoculated 10 times with 10 mg bacterial wet mass of MAP (total dose 2.6 × 10(8) colony-forming units). Six to 7 inoculated goats and 3 controls were autopsied 3, 6, 9, and 12 months postinoculation (mpi), lesions were documented, and samples were collected for histology, immunohistochemistry (IHC), and bacterial culture. Twenty-five of the 26 inoculated goats did not develop clinical signs. Macroscopic lesions were detected in 3 of the 7 inoculated goats as soon as 3 mpi. Jejunal Peyer's patches (JPPs) were thickened and had ulcerated surfaces and circumscribed serositis. Characteristic granulomatous infiltrates were seen in all goats in gut-associated lymphoid tissues (GALTs), especially JPPs and lymphoid tissue at the ileocecal valve and in intestinal lymph nodes. Granulomatous intestinal infiltrates not associated with GALT were seen beginning at 6 mpi and with increasing frequency thereafter. Interindividual differences in lesions were most pronounced at 12 mpi, varying from mild focal paucibacillary to severe diffuse multibacillary patterns. Bacterial culture of MAP confirmed the IHC findings but was more sensitive and revealed widespread dissemination at 3 and 12 mpi. Granulomatous arteritis was found in intestinal submucosa of several goats. This may contribute to the spreading of MAP to the intestinal wall and possibly systemically. The different lesions observed during the clinically inapparent period of paratuberculosis are most likely indicators for the later progression of infection and development of clinical disease.
“…Macroscopic lesions occurred as early as 3 mpi predominantly in JPPs that were firm and thickened by granulomatous infiltration and had ulcerated surfaces. Mucosal ulcerations have been described in cases of naturally infected goats with diffuse intestinal lesions 19,24 and after experimental infection of goats with a mycobacterium isolated from patients with Crohn's disease. 42 The ulcerations we observed were frequently accompanied by transmural inflammation, resulting in foci of circumscribed serositis along the small intestine.…”
Section: Discussionmentioning
confidence: 99%
“…These may be the sites of origin of the strictures described in naturally infected goats. 19 The serositis facilitated a precise collection of altered intestine.…”
Section: Discussionmentioning
confidence: 99%
“…20 Variable findings have been reported concerning the preferential sites of lesions in the intestine of goats with paratuberculosis. Several studies found the jejunum most severely affected, 19,20,36,41 whereas others noted the distal small intestine. 25,40 In our investigation, predominantly JPPs in the proximal and mid-jejunum and the ICVPP were altered in subclinical paratuberculosis.…”
The development of lesions after infection with Mycobacterium avium subsp paratuberculosis (MAP) was examined in an experimental infection model. Goat kids were orally inoculated 10 times with 10 mg bacterial wet mass of MAP (total dose 2.6 × 10(8) colony-forming units). Six to 7 inoculated goats and 3 controls were autopsied 3, 6, 9, and 12 months postinoculation (mpi), lesions were documented, and samples were collected for histology, immunohistochemistry (IHC), and bacterial culture. Twenty-five of the 26 inoculated goats did not develop clinical signs. Macroscopic lesions were detected in 3 of the 7 inoculated goats as soon as 3 mpi. Jejunal Peyer's patches (JPPs) were thickened and had ulcerated surfaces and circumscribed serositis. Characteristic granulomatous infiltrates were seen in all goats in gut-associated lymphoid tissues (GALTs), especially JPPs and lymphoid tissue at the ileocecal valve and in intestinal lymph nodes. Granulomatous intestinal infiltrates not associated with GALT were seen beginning at 6 mpi and with increasing frequency thereafter. Interindividual differences in lesions were most pronounced at 12 mpi, varying from mild focal paucibacillary to severe diffuse multibacillary patterns. Bacterial culture of MAP confirmed the IHC findings but was more sensitive and revealed widespread dissemination at 3 and 12 mpi. Granulomatous arteritis was found in intestinal submucosa of several goats. This may contribute to the spreading of MAP to the intestinal wall and possibly systemically. The different lesions observed during the clinically inapparent period of paratuberculosis are most likely indicators for the later progression of infection and development of clinical disease.
“…All of these cells migrated to the area of transplantation surgery trauma and specifically to the foreign microcapsules. Once at these sites, the immune cells activated stromal cells, endothelial cells, and fibroblasts to form cell adhesions to the microcapsules and finally returned to initial equilibrium states . Our study has shown that macrophages and leukocytes have a positive correlation with the level of adhesion, and neutrophils did not correlate with the level of adhesion.…”
Section: Discussionmentioning
confidence: 54%
“…As with macrophages, IL‐6 performed a proinflammatory function and resulted in cell adhesion on the microcapsules. IL‐10 is an anti‐inflammatory cytokine, and is primarily produced by monocytes, mast cells and lymphocytes . It down regulates the expression of Th1 cytokines and counteracts the inflammatory effect.…”
Cell microencapsulation technology is a potential alternative therapy, but cell overgrowth and adhesion on the microcapsules after transplantation shortens their time of therapeutic efficacy. Inflammatory cells were the main cells that adhered to the microcapsules, so understanding the body's inflammatory processes would help to better identify the mechanisms of cell adhesion to the outer surface of the microcapsules. Our study measured the inflammatory cells and the cytokines and characterized the associated changes in the alginate-chitosan-alginate (ACA) microcapsules 1, 7, 14, and 28 days after implantation in the peritoneal cavity. Then the relationship between the inflammatory response and cell adhesion on the microcapsules was evaluated by multiple regression analysis. The results showed that the microcapsules did not evoke a systemic inflammatory response, but initiated a local inflammatory response in the peritoneal cavity. Furthermore, the correlation analysis showed that the level of cell adhesion on the microcapsules was related to the number of lymphocytes and macrophages, and the amount of IL-6, IL-10, and MCP-1 in the peritoneal cavity. Our results may provide a foundation for reducing the immune response to these microcapsules, prolonging graft survival and improving the efficacy of these treatments.
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