Defective macrophage handling of Escherichia coli in Crohn's disease. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: Elliott, TR; Hudspith, BN; Rayment, NB; Prescott, NJ; Petrovska, L; Hermon‐Taylor, J; Brostoff, J; Boussioutas, A; Mathew, CG; Sanderson, JD
• Is Part Of: Journal of gastroenterology and hepatology. Volume 30:Issue 8(2015:Aug.)
• Page Start: 1265
• Page End: 1274
• Publication Date: 2015-08
• Subjects: Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Liver Diseases -- Periodicals; 616.33
• DOI: 10.1111/jgh.12955
• Languages: English
• ISSNs: 0815-9319

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jgh12955-sec-0001" sec-type="section"> <title>Background and Aim</title> <p> <italic>E</italic><italic>scherichia coli</italic> can be isolated from lamina propria macrophages in Crohn's disease (CD), and their intramacrophage persistence may provide a stimulus for inflammation. To further determine the contributions of macrophage dysfunction and <italic>E</italic><italic>. coli</italic> pathogenicity to this, we aimed to compare <italic>in vitro</italic> functioning of macrophages from patients with CD and healthy controls (HC) in response to infection with CD‐derived adherent‐invasive <italic>E</italic><italic>. coli</italic> (AIEC) and less pathogenic <italic>E</italic><italic>. coli</italic> strains.</p> </sec> <sec id="jgh12955-sec-0002" sec-type="section"> <title>Methods</title> <p> Monocyte‐derived macrophages were cultured from patients with CD and HC. Intramacrophage survival of <italic>E</italic><italic>. coli</italic> strains (CD‐derived adherent‐invasive [AI] and non‐AI strains and laboratory strain K‐12) was compared. Macrophage cytokine release (tumor necrosis factor alpha [TNFα], interleukin [IL]‐23, IL‐8 and IL‐10) and monocyte phagoctyosis and respiratory burst function were measured after <italic>E</italic><italic>. coli</italic> infection. For CD patients, laboratory data were correlated with clinical phenotype, use of immunomodulation, and CD risk alleles (<italic>NOD2</italic>, <italic>IL‐23R</italic>, <italic>ATG16L1</italic> and <italic>IRGM</italic>).</p> </sec> <sec id="jgh12955-sec-0003" sec-type="section"> <title>Results</title> <p> Attenuated TNFα and IL‐23 release from CD macrophages was found after infection with all <italic>E</italic><italic>. coli</italic> strains. There was prolonged survival of CD‐derived AIEC, CD‐derived non‐AIEC and <italic>E</italic><italic>. coli</italic> K‐12 in macrophages from CD patients compared to within those from HC. No abnormality of monocyte phagocytosis or respiratory burst function was detected in CD. Macrophage dysfunction in CD was not influenced by phenotype, use of immunomodulation or genotype.</p> </sec> <sec id="jgh12955-sec-0004" sec-type="section"> <title>Conclusions</title> <p> CD macrophage responses to infection with <italic>E</italic><italic>. coli</italic> are deficient, regardless of clinical phenotype, CD genotype or <italic>E</italic><italic>. coli</italic> pathogenicity. This suggests host immunodeficiency is an important contributor to intramacrophage <italic>E</italic><italic>. coli</italic> persistence in CD.</p> </sec> </abstract>