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Mycobacterium avium subsp. Paratuberculosis (MAP) as a modifying factor in Crohn's disease
Shomik Sibartie1, Paul Scully, John Keohane
1Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland.
Background:
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).
Methods:
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).
Results:
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.
Conclusions:
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.
Insights
Crohn's disease patients show increased T-cell proliferation and altered cytokine responses to Mycobacterium avium subspecies paratuberculosis (MAP). This suggests MAP may be an environmental factor influencing the immune system in Crohn's disease.
Area of Science:
- Immunology
- Gastroenterology
- Microbiology
Background:
- Crohn's disease (CD) is a complex condition with genetic and environmental factors.
- Mycobacterium avium subspecies paratuberculosis (MAP) is often found in CD tissues, but its role in immune response is unclear.
Purpose of the Study:
- To investigate the impact of MAP on T-cell proliferation and cytokine production in patients with inflammatory bowel disease (IBD).
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph node cells (MLNCs) were collected from IBD patients and controls.
- T-cell proliferation was measured using flow cytometry after MAP exposure.
- Cytokine profiles were analyzed in response to MAP, Listeria monocytogenes (LM), and Salmonella typhimurium (ST).
Main Results:
- PBMCs from CD patients exhibited significantly higher T-cell proliferation in response to MAP compared to ulcerative colitis (UC) patients and healthy controls.
- CD patient PBMCs secreted elevated levels of TNF-alpha and IL-10 when exposed to MAP.
- MLNCs from both CD and UC patients showed increased TNF-alpha and IL-8 production in response to MAP.
Conclusions:
- Elevated T-cell proliferation and altered cytokine profiles in CD patients suggest immune system engagement with MAP.
- These findings support further research into MAP as a potential environmental factor in Crohn's disease pathogenesis.
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