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Intestinal recruiting and activation profiles in peripheral blood mononuclear cells in response to pathogen‐associated molecular patterns stimulation in patients with IBS
Author(s) -
RodríguezFandiño O.,
HernándezRuíz J.,
LópezVidal Y.,
Charúa L.,
BandehMoghaddam H.,
Minzoni A.,
Guzmán C.,
Schmulson M.
Publication year - 2013
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12204
Subject(s) - peripheral blood mononuclear cell , chemokine , lipopolysaccharide , immunology , immune system , stimulation , cd8 , medicine , biology , in vitro , biochemistry
Background Immune activation, increased Toll‐like Receptors ( TLR ) expression, and gut epithelial diffusion of bacterial molecules have been reported in irritable bowel syndrome ( IBS ). Thus, we sought to relate these factors by analyzing gut homing (integrin α4β7), intestinal recruiting ( CCR 5) and activation ( CD 28) phenotypes, and the cytokines and chemokines concentration in peripheral blood T‐lymphocytes stimulated with TLR ‐ligands. Methods Twenty‐one IBS ‐Rome II (1 PI ‐ IBS ) patients and 19 controls were studied. Isolated peripheral blood mononuclear cells were cultured with and without E scherichia coli lipopolysaccharide ( LPS ), S taphylococcus aureus peptidoglycan ( PGN ), and unmethylated cytosine‐phosphate‐guanine motifs (CpG). Phenotypes were investigated by flow cytometry and supernatant cytokines and chemokines were also measured. Key Results After LPS , CCR 5 expression in CD4 + α4β7 + cells remained unchanged in IBS , but decreased in controls ( p = 0.002), to lower levels than in IBS (Mean fluorescence intensity [ MFI ]: 1590 ± 126.9 vs 2417 ± 88.4, p < 0.001). There were less CD8 + α4β7 + CCR5 + cells (85.7 ± 1.5 vs 90.8 ± 0.9%, p = 0.006) after LPS and CD3 + α4β7 + CCR5 + (40.0 ± 1.7 vs 51.2 ± 4.3%, p = 0.006) after PGN in controls. Also, after LPS , CD28 decreased in CD4 + α4β7 + CCR5 + in IBS ( MFI : 2337 ± 47.2 vs 1779 ± 179.2, p < 0.001), but not in controls. Cytokines and chemokines were similar, except for lower IL 8/ CXCL 8 in the unstimulated condition in IBS (4.18, 95% CI : 3.94–4.42 vs 3.77, 3.59–3.95; p = 0.006). Conclusions & Inferences Pathogen‐associated molecular patterns stimulation of peripheral blood T cells expressing gut homing marker in IBS compared with controls resulted in an unsuccessful down‐regulation of the co‐expression of intestinal recruiting/residence phenotype and a state of activation. These findings support an interaction between an innate immune predisposition and microbial triggers, which may unleash or exacerbate IBS .