Macrophages from IBD patients exhibit defective tumour necrosis factor-alpha secretion but otherwise normal or augmented pro-inflammatory responses to infection

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Nair Campos (Author) Other; Fernando Magro (Author) FMUP; Ana Rita Castro (Author) Other; Joana Cabral (Author) Other; Pedro Rodrigues (Author) Other; Ricardo Silva (Author) Other; Rui Appelberg (Author) ICBAS; Susana Rodrigues (Author) Other; Susana Lopes (Author) Other; Guilherme Macedo (Author) FMUP; Amelia Sarmento (Author) Other

Journal

Title: Immunobiology

Vol. 216

Pages: 961-970

ISSN: 0171-2985

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 29 Citations

Scopus - 32 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-P6S

DOI: 10.1016/j.imbio.2011.01.002

Abstract (EN): 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 coil or Enterococcus faecalis, cytokine levels and cell surface receptor expression were evaluated at different time points. Macrophages from CD patients showed impaired TNF-alpha 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-alpha 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10