Mycobacterium avium subsp. Paratuberculosis (MAP) as a modifying factor in Crohn's disease.
Sibartie, Shomik Scully, Paul Keohane, John O'Neill, Shaun O'Mahony, Jim O'Hanlon, Deirdre Kirwan, William O O'Mahony, Liam Shanahan, Fergus
Sibartie, Shomik
Scully, Paul
Keohane, John
O'Neill, Shaun
O'Mahony, Jim
O'Hanlon, Deirdre
Kirwan, William O
O'Mahony, Liam
Shanahan, Fergus
Advisors
Editors
Other Contributors
Date
2010-02
Date Submitted
Keywords
Other Subjects
Subject Mesh
Adolescent
Adult
Aged
Aged, 80 and over
Crohn Disease
Cytokines
Female
Humans
Interleukin-10
Lymphocyte Activation
Male
Middle Aged
Mycobacterium avium subsp. paratuberculosis
Paratuberculosis
T-Lymphocytes
Tumor Necrosis Factor-alpha
Young Adult
Adult
Aged
Aged, 80 and over
Crohn Disease
Cytokines
Female
Humans
Interleukin-10
Lymphocyte Activation
Male
Middle Aged
Mycobacterium avium subsp. paratuberculosis
Paratuberculosis
T-Lymphocytes
Tumor Necrosis Factor-alpha
Young Adult
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
Crohn's disease (CD) is a multifactorial syndrome with genetic and environmental contributions. Mycobacterium avium subspecies paratuberculosis (MAP) has been frequently isolated from mucosal tissues of patients with CD but the cellular immune response to this bacterium has been poorly described. Our aim was to examine the influence of MAP on T-cell proliferation and cytokine responses in patients with inflammatory bowel disease (IBD).
Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph node cells (MLNCs) were obtained from IBD patients and non-IBD controls. PBMC T-cell proliferation in response to MAP was determined using CFSE labeling and flow cytometry. The specificity of cytokine responses to MAP was controlled by parallel exposure to Listeria monocytogenes (LM) or Salmonella typhimurium (ST).
Coincubation of PBMCs with MAP induced significantly more T-cell proliferation (P < 0.0001) in PBMCs isolated from CD patients compared to PBMCs obtained from ulcerative colitis (UC) patients or healthy volunteers. In addition, PBMCs from CD patients secreted significantly higher (P < 0.05) levels of tumor necrosis factor-alpha (TNF-alpha; 2302 +/- 230 pg/mL) and interleukin (IL)-10 (299 +/- 48 pg/mL) in response to MAP compared to UC patients (TNF-alpha: 1219 +/- 411 pg/mL; IL-10: 125 +/- 19 pg/mL) and controls (TNF-alpha: 1447 +/- 173 pg/mL; IL-10: 127 +/- 12 pg/mL). No difference in cytokine responses was observed in response to LM or ST. MLNCs from both CD and UC patients secreted significantly more TNF-alpha and IL-8 in response to MAP compared to MLNCs from non-IBD control patients.
Increased proliferation of T cells and an altered cytokine response suggest that prior exposure to MAP and engagement of the immune system is common in patients with CD. This does not imply causation but does support further examination of this bacterium as an environmental modifying factor.
Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph node cells (MLNCs) were obtained from IBD patients and non-IBD controls. PBMC T-cell proliferation in response to MAP was determined using CFSE labeling and flow cytometry. The specificity of cytokine responses to MAP was controlled by parallel exposure to Listeria monocytogenes (LM) or Salmonella typhimurium (ST).
Coincubation of PBMCs with MAP induced significantly more T-cell proliferation (P < 0.0001) in PBMCs isolated from CD patients compared to PBMCs obtained from ulcerative colitis (UC) patients or healthy volunteers. In addition, PBMCs from CD patients secreted significantly higher (P < 0.05) levels of tumor necrosis factor-alpha (TNF-alpha; 2302 +/- 230 pg/mL) and interleukin (IL)-10 (299 +/- 48 pg/mL) in response to MAP compared to UC patients (TNF-alpha: 1219 +/- 411 pg/mL; IL-10: 125 +/- 19 pg/mL) and controls (TNF-alpha: 1447 +/- 173 pg/mL; IL-10: 127 +/- 12 pg/mL). No difference in cytokine responses was observed in response to LM or ST. MLNCs from both CD and UC patients secreted significantly more TNF-alpha and IL-8 in response to MAP compared to MLNCs from non-IBD control patients.
Increased proliferation of T cells and an altered cytokine response suggest that prior exposure to MAP and engagement of the immune system is common in patients with CD. This does not imply causation but does support further examination of this bacterium as an environmental modifying factor.
Language
en
ISSN
1536-4844
eISSN
ISBN
DOI
10.1002/ibd.21052
PMID
19824071