Intestinal macrophages: differentiation and involvement in intestinal immunopathologies

Abstract

Intestinal macrophages, preferentially located in the subepithelial lamina propria, represent the largest pool of tissue macrophages in humans. As an adaptation to the local antigen-and bacteria-rich environment, intestinal macrophages exhibit several distinct phenotypic and functional characteristics. Notably, microbe-associated molecular pattern receptors, including the lipopolysaccharide (LPS) receptors CD14 and TLR4, and also the Fc receptors for IgA and IgG are absent on most intestinal macrophages under homeostatic conditions. Moreover, while macrophages in the intestinal mucosa are refractory to the induction of proinflammatory cytokine secretion, they still display potent phagocytic activity. These adaptations allow intestinal macrophages to comply with their main task, i.e., the efficient removal of microbes while maintaining local tissue homeostasis. In this paper, we review recent findings on the functional differentiation of monocyte subsets into distinct macrophage populations and on the phenotypic and functional adaptations that have evolved in intestinal macrophages in response to their antigen-rich environment. Furthermore, the involvement of intestinal macrophages in the pathogenesis of celiac disease and inflammatory bowel diseases is discussed.

Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states

“…17 The strong correlation between the monocyte/macrophage enhancer signature with SNPs associated with ulcerative colitis, celiac disease, Crohn disease, or systemic lupus erythematosus is entirely consistent with the proposed role of human monocytes and macrophages in these diseases 14,48 and also confirms a previous, similar approach analyzing several cell lines. 49 Linking GWAS data with epigenetic enhancer signatures of different cell types could thus present an important step toward a functional annotation of noncoding disease variants.…”

“…Sequence tags from different donors were combined and tag counts were normalized to 10 7 specifically mapped tags. Published ChIP-sequencing (ChIP-seq) data for CD133 ϩ hematopoietic stem cells (HSCs) 15 were remapped from raw sequence data to the GRCh37/hg19 assembly using Bowtie, 14 and local tag counts were normalized for GC nucleotide content to match the corresponding monocyte datasets using HOMER. 8 A summary of the ChIP-seq data used in this study is provided in supplemental Table 1.…”

“…ChIP fragments were sequenced for 36 cycles on Illumina Genome Analyzers I or II according to the manufacturer's instructions. Sequence tags were mapped to the current human reference sequence (GRCh37/hg19) using Bowtie 14 and only uniquely mapped tags were used for downstream analyses. Sequence tags from different donors were combined and tag counts were normalized to 10 7 specifically mapped tags.…”

Nonpathogenic Lactobacillus rhamnosus activates the inflammasome and antiviral responses in human macrophages

“…The studies performed with human intestinal macrophages originating from subepithelial lamina propria are few, and limited to observations made in vitro. 28 Human intestinal macrophages have been demonstrated to display inability to mount an inflammatory response while retaining the ability to phagocytose microbes. 29 However, CD14 + lamina propria macrophages have been shown to induce pro-inflammatory cytokines including IL-1β and IL-6 30,31 indicating that intestinal macrophage population is not exclusively anti-inflammatory.…”

Small Molecule Tyrosine Kinase Inhibitors for the Treatment of Intestinal Inflammation

“…Mononuclear phagocyte numbers increase in the inflamed intestinal mucosa of patients with active IBD and a significant positive correlation has been noted between the number of infiltrating intestinal mononuclear phagocytes and the degree of crypt inflammation in UC. 24 Further studies will help delineate the differences in the mechanisms of action of the two compounds and aid in the elucidation of additional application for inflammatory disease with distinct underlying immunoregulatory deficiencies.…”