Development of a Bovine Ileal Cannulation Model To Study the Immune Response and Mechanisms of Pathogenesis of Paratuberculosis

Allen, Andrew J.; Park, Kun Taek; Barrington, George M.; Lahmers, Kevin K.; Hamilton, Mary Jo; Davis, William C.

doi:10.1128/cvi.00347-08

Cited by 42 publications

(72 citation statements)

References 42 publications

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“…Rare Map-infected macrophages were observed in the intestinal propria within 24 hours after oral infection, and Map DNA was identified using PCR in sequentially biopsied intestinal tissues; however, significant differences in the activation status of intraepithelial lymphocytes of infected versus uninfected animals were not demonstrated in the study. 1 The characteristic Map-induced lesions, acid-fast organisms, and active fecal shedding of Map have not been observed in either the ligated intestinal loop or ileal cannulation models. Regardless, a clear advantage of intestinal loop, ileal cannulation, and oral infection models is the ability to potentially investigate interactions of live Map with intestinal epithelia and/or M cells, which are proposed to play a significant but incompletely explored role in the pathogenesis of natural infection.…”

Section: Discussionmentioning

confidence: 99%

“…1,7 The classic immunologic paradigm associated with mycobacterial disease is biphasic and characterized by an initial T-helper 1 (Th1) response. Effective Th1 polarization mediated by IFNg is considered to be integral for controlling mycobacterial infections, 18 and detection of Map-specific IFNg has been successfully used diagnostically during early stages of mycobacterial disease including Map infection in cattle.…”

Section: Discussionmentioning

confidence: 99%

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Direct Inoculation of Mycobacteriumavium Subspecies Paratuberculosis Into Ileocecal Peyer’s Patches Results in Colonization of the Intestine in a Calf Model

et al. 2010

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The objective of this study was to develop an intestinal model of Mycobacterium avium subspecies paratuberculosis (Map) infection in the calf for evaluation of mucosal pathology and local and systemic immunologic responses. Map was inoculated into Peyer's patches of young calves using a right flank surgical approach in standing calves to exteriorize the ileocecal junction. Inoculum doses ranging from 10 3 to 10 9 colony-forming units of strain K10 Map were injected through the serosal surface into Peyer's patches of the distal ileum near the ileocecal valve. Fecal samples were collected for culture from each calf weekly until termination of the study. Calves were necropsied at 7, 30, 60, and 90 days after infection, when inoculation sites, lymph nodes, spleen, and peripheral blood were collected for evaluation. Ileocecal lymph nodes were consistently colonized by Map in the 10 5 to 10 9 groups. The ileocecal valve was also colonized in 10 7 and 10 9 groups. This correlated with fecal culture results as infected calves intermittently shed Map in their feces throughout the study. Granulomatous lesions with giant cells and acid-fast bacilli at the ileocecal junction, ileocecal lymph nodes, and lamina propria of high-dose animals (10 7 and 10 9 ) were identified from each time point. Flow cytometry was used to detect antigen-specific production of interferon-g and interleukin-4 locally (ileocecal lymph node) and systemically (peripheral blood mononuclear cells), which defined distinct immunologic profiles in low-dose and high-dose calves. This study demonstrates intestinal Map infection via Peyer's patch inoculation, a novel model with many shared features of natural Map infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Direct Inoculation of Mycobacteriumavium Subspecies Paratuberculosis Into Ileocecal Peyer’s Patches Results in Colonization of the Intestine in a Calf Model

et al. 2010

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“…Studies have characterized host-pathogen interactions when M. avium subsp. paratuberculosis infection is first established (8,23), and more recently, models have been developed to monitor host responses during persistent infections (24,25). With these models, however, it was not possible to ensure that M. avium subsp.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, an ileal cannulation model that facilitated the repeated delivery of a defined dose of M. avium subsp. paratuberculosis to the terminal small intestine was developed for 8-to 9-week-old calves (25). These models were limited, however, by variable uptake of M. avium subsp.…”

mentioning

confidence: 99%

Host Responses to Persistent Mycobacterium avium Subspecies paratuberculosis Infection in Surgically Isolated Bovine Ileal Segments

Charavaryamath

González-Cano

Fries

et al. 2013

Clin Vaccine Immunol

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A lack of appropriate disease models has limited our understanding of the pathogenesis of persistent enteric infections with Mycobacterium avium subsp. paratuberculosis. A model was developed for the controlled delivery of a defined dose of M. avium subsp. paratuberculosis to surgically isolated ileal segments in newborn calves. The stable intestinal segments enabled the characterization of host responses to persistent M. avium subsp. paratuberculosis infections after a 9-month period, including an analysis of local mucosal immune responses relative to an adjacent uninfected intestinal compartment. M. avium subsp. paratuberculosis remained localized at the initial site of intestinal infection and was not detected by PCR in the mesenteric lymph node. M. avium subsp. paratuberculosis-specific T cell proliferative responses included both CD4 and ␥␦ T cell receptor (␥␦TcR) T cell responses in the draining mesenteric lymph node. The levels of CD8 ؉ and ␥␦TcR ؉ T cells increased significantly (P < 0.05) in the lamina propria, and M. avium subsp. paratuberculosis-specific tumor necrosis factor alpha (TNF-␣) and gamma interferon secretion by lamina propria leukocytes was also significantly (P < 0.05) increased. There was a significant (P < 0.05) accumulation of macrophages and dendritic cells (DCs) in the lamina propria, but the expression of mucosal toll-like receptors 1 through 10 was not significantly changed by M. avium subsp. paratuberculosis infection. In conclusion, surgically isolated ileal segments provided a model system for the establishment of a persistent and localized enteric M. avium subsp. paratuberculosis infection in cattle and facilitated the analysis of M. avium subsp. paratuberculosis-specific changes in mucosal leukocyte phenotype and function. The accumulation of DC subpopulations in the lamina propria suggests that further investigation of mucosal DCs may provide insight into host responses to M. avium subsp. paratuberculosis infection and improve vaccine strategies to prevent M. avium subsp. paratuberculosis infection.

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“…This knowledge gap has driven recent development of novel modeling systems in cattle with the goal of clarifying factors that may shape development and progression of disease. 1,12,22 The importance of initial host-pathogen interactions are well recognized, 28 and the goal of this study was to evaluate early gamma-delta (gd) T-cell responses at subcutaneous Map challenge sites in calves. Natural Map infection is an intestinal disease, and clearly, a subcutaneous model is not without limitations; however, we believe that the model is useful to study antimycobacterial host responses at early infection sites.…”

mentioning

confidence: 99%

Gamma-Delta T-Cell Responses During SubcutaneousMycobacterium aviumSubspeciesparatuberculosisChallenge in Sensitized or Naïve Calves Using Matrix Biopolymers

2012

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We have developed a model to explore the early immune response against Mycobacterium avium subspecies paratuberculosis (Map) infection in the bovine calf using subcutaneously placed liquid gel matrix biopolymer (matrigel) containing live Map. Matrigel rapidly polymerizes in vivo, retains recruited cellular infiltrates and soluble immune mediators, and can be rapidly removed 48 hours later and depolymerized for analysis. In this study, we examined early host immune events at matrigel/Map sites; recruited cells were evaluated by histopathology and flow cytometry, and cytokines were measured by flow cytometry, enzymelinked immunosorbent assay, and Luminex bead immunoassay. Our results demonstrate earlier recruitment of gamma-delta (gd) T cells to matrigel/Map challenge sites compared to CD4þ T cells. We also show that significantly more gd T cells were recruited to matrigel/Map sites postinfection day 7 compared to postinfection day 30 and that these cells produced significant amounts of the cytokine interferon gamma. We also provide evidence that peripheral blood-derived gd T-cell subsets in cattle differentially generate interferon gamma, suggesting distinct roles for these cells. These data provide unique insight into initial antimycobacterial host cellular immune responses following Map infection in calves.

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Development of a Bovine Ileal Cannulation Model To Study the Immune Response and Mechanisms of Pathogenesis of Paratuberculosis

Cited by 42 publications

References 42 publications

Direct Inoculation of Mycobacteriumavium Subspecies Paratuberculosis Into Ileocecal Peyer’s Patches Results in Colonization of the Intestine in a Calf Model

Direct Inoculation of Mycobacteriumavium Subspecies Paratuberculosis Into Ileocecal Peyer’s Patches Results in Colonization of the Intestine in a Calf Model

Host Responses to Persistent Mycobacterium avium Subspecies paratuberculosis Infection in Surgically Isolated Bovine Ileal Segments

Gamma-Delta T-Cell Responses During SubcutaneousMycobacterium aviumSubspeciesparatuberculosisChallenge in Sensitized or Naïve Calves Using Matrix Biopolymers

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