Macrophages from IBD patients exhibit defective tumour necrosis factor-α secretion but otherwise normal or augmented pro-inflammatory responses to infection.
Defects in macrophage function have been implicated in the establishment of Crohn's disease (CD). However, the response of macrophages from CD patients to live bacteria, particularly Mycobacterium avium subsp. paratuberculosis (MAP), has not been addressed. Considering MAP has long been associated to CD, our objective was to assess whether macrophages from CD patients showed impaired inflammatory response to infection by MAP comparing to M. avium subsp. avium (MA) and other live intestinal commensal bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, ulcerative colitis (UC) patients and controls. Following in vitro infection with MAP, MA, Escherichia coli or Enterococcus faecalis, cytokine levels and cell surface receptor expression were evaluated at different time points. Macrophages from CD patients showed impaired TNF-α secretion in response to bacterial challenge, but augmented IL-23 secretion and preserved IL-12 secretion and CD-40 expression. In addition, CD macrophages showed low IL-10 secretion. Macrophages from IBD patients showed increased expression of TLR-2 and -4, unaffected by infection. Differences in cytokine secretion observed after bacterial challenge were not MAP-specific, as other bacteria (E. coli and MA) showed similar effects. Macrophages from UC patients showed a less compromised TNF-α synthesis in response to mycobacterial infection than CD macrophages, with increased constitutive IL-12 secretion, and preserved IL-10 secretion. The increased IL-23 levels in response to infection and decreased IL-10 production observed in macrophages from CD patients may contribute to the inflammatory exacerbation observed in those patients.
CEBIMED - Biomedicine Research Center, Health Sciences Faculty, University Fernando Pessoa, Porto, Portugal.
Nair
N
Campos
Fernando
F
Magro
Ana Rita
AR
Castro
Joana
J
Cabral
Pedro
P
Rodrigues
Ricardo
R
Silva
Rui
R
Appelberg
Susana
S
Rodrigues
Susana
S
Lopes
Guilherme
G
Macedo
Amélia
A
Sarmento
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D003424:Crohn Disease / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D013293:Enterococcus faecalis / Q000254:growth & development; D004926:Escherichia coli / Q000254:growth & development; D004927:Escherichia coli Infections / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007109:Immunity; D007249:Inflammation / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism; D053759:Interleukin-23 / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009162:Mycobacterium avium / Q000254:growth & development; D016927:Mycobacterium avium subsp. paratuberculosis / Q000254:growth & development; D010283:Paratuberculosis / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha
D053759:Interleukin-23; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12