Maturation Phenotype of Peripheral Blood Monocyte/Macrophage After Stimulation with Lipopolysaccharides in Irritable Bowel Syndrome

Abstract

Background/AimsAbnormal immune regulation and increased intestinal permeability augmenting the passage of bacterial molecules that can activate immune cells, such as monocytes/macrophages, have been reported in irritable bowel syndrome (IBS). The aim was to compare the maturation phenotype of monocytes/macrophages (CD14+) from IBS patients and controls in the presence or absence of Escherichia coli lipopolysaccharides (LPS), in vitro. MethodsMononuclear cells were isolated from peripheral blood of 20 Rome II-IBS patients and 19 controls and cultured with or without LPS for 72 hours. The maturation phenotype was examined by flow cytometry as follows: M1-Early (CD11c + CD206 -), M2-Advanced (CD11c -CD206 + CX3CR1 + ); expression of membrane markers was reported as mean fluorescence intensity (MFI). The Mann-Whitney test was used and significance was set at P < 0.05. ResultsIn CD14+ cells, CD11c expression decreased with vs without LPS both in IBS (MFI: 8766.0 ± 730.2 vs 12 920.0 ± 949.2, P < 0.001) and controls (8233.0 ± 613.9 vs 13 750.0 ± 743.3, P < 0.001). M1-Early cells without LPS, showed lower CD11c expression in IBS than controls (MFI: 11 540.0 ± 537.5 vs 13 860.0 ± 893.7, P = 0.040), while both groups showed less CD11c in response to LPS (P < 0.01). Furthermore, the percentage of "Intermediate" (CD11c + CD206 + CX3CR1 + ) cells without LPS, was higher in IBS than controls (IBS = 9.5 ± 1.5% vs C = 4.9 ± 1.4%, P < 0.001). Finally, fractalkine receptor (CX3CR1) expression on M2-Advanced cells was increased when treated with LPS in controls but not in IBS (P < 0.001). ConclusionsThe initial phase of monocyte/macrophage maturation appears to be more advanced in IBS compared to controls. However, the decreased CX3CR1 in patients with IBS, compared to controls, when stimulated with LPS suggests a state of immune activation in IBS.

Enteric Glia Modulate Macrophage Phenotype and Visceral Sensitivity following Inflammation

“…Macrophage maturation is defective in IBD and IBS ( Baillie et al, 2017 ; Rodríguez-Fandiño et al, 2017 ), and strategies that modulate this process could have broad therapeutic relevance. M-CSF influences several essential functions of macrophages including survival, proliferation, chemotaxis, and activation ( Pixley and Stanley, 2004 ).…”

“…Abdominal pain is the leading gastrointestinal (GI) symptom in the United States and is the dominant symptom of bowel disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) ( Chang et al, 2018 ; Lee et al, 2017a ; Mearin et al, 2016 ; Peery et al, 2015 ; Rodríguez-Fandiño et al, 2017 ). Nociceptor sensitivity is the most important factor that gates the transmission of noxious information from the intestine to the brain, and processes that alter nociceptor sensitivity in the periphery play a fundamental role in the generation of abdominal pain and the transition from acute to chronic pain ( Brierley and Linden, 2014 ).…”

The enteric nervous system in gastrointestinal disease etiology

“…As targets of a vagal-cholinergic enteric neuron antiinflammatory pathway [144], and in keeping with their vital role in ENS survival and function [145,146], this data touts that muscularis macrophages can temper with the entericinflammasome circuit and ergo, prevent remolding of the neurochemical representation of enteric neurons. Defective maturation and altered numbers of macrophages have been documented in IBS [147,148]. Among other functions, macrophage-colony stimulating factor (M-CSF) governs survival, proliferation, and activation of macrophages, and while interstitial cells of Cajal also produce M-CSF, within the ENS, EGCs generate the vast majority of M-CSF [149][150][151].…”

Immune activation in irritable bowel syndrome: from basic to clinic

“…Akbar et al 42 Mast cells; T-cells RS Bian et al 65 Mast cells DC Balestra et al 43 Mast cells DC Barbara et al 44 Mast cells DC Barbara et al 45 Mast cells DC 70 . Regional mast cell activation has also been shown in IBS.…”

“…Of note, matured macrophages could be a source for immune signaling molecules such as TNF-α in these patients. 70 Therefore, there is a very mild form of inflammation in IBS. We need to understand whether this form of inflammation could be translated into non-invasive inflammatory biomarkers such as acute-phase reactants in the blood or stool of IBS patients.…”