Mycobacterium avium subsp. Paratuberculosis (MAP) as a modifying factor in Crohn's disease.
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.
Sibartie
Shomik
S
Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland.
Scully
Paul
P
Keohane
John
J
O'Neill
Shaun
S
O'Mahony
Jim
J
O'Hanlon
Deirdre
D
Kirwan
William O
WO
O'Mahony
Liam
L
Shanahan
Fergus
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003424:Crohn Disease / Q000150:complications / Q000276:immunology / Q000382:microbiology*; D016207:Cytokines / Q000097:blood / Q000502:physiology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016927:Mycobacterium avium subsp. paratuberculosis; D010283:Paratuberculosis / Q000150:complications* / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000502:physiology; D055815:Young Adult
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10