Intestinal recruiting and activation profiles in peripheral blood mononuclear cells in response to pathogen-associated molecular patterns stimulation in patients with IBS

Authors

  • O. Rodríguez-Fandiño,

    1. Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Departamento de Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM), Hospital General de México, México Distrito Federal, México
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  • J. Hernández-Ruíz,

    1. Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Departamento de Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM), Hospital General de México, México Distrito Federal, México
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  • Y. López-Vidal,

    1. Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, México Distrito Federal, México
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  • L. Charúa,

    1. Unidad de Coloproctología, Hospital General de México, México Distrito Federal, México
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  • H. Bandeh-Moghaddam,

    1. Unidad de Coloproctología, Hospital General de México, México Distrito Federal, México
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  • A. Minzoni,

    1. Departamento de Matemáticas y Mecánica, Instituto de Investigación en Matemáticas Aplicadas y Sistemas, Universidad Nacional Autónoma de México, México Distrito Federal, México
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  • C. Guzmán,

    1. Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Departamento de Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM), Hospital General de México, México Distrito Federal, México
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  • M. Schmulson

    Corresponding author
    • Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Departamento de Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM), Hospital General de México, México Distrito Federal, México
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Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 26, Issue 6, 891, Article first published online: 23 May 2014

Address for Correspondence

Max Schmulson, Laboratorio de Hígado, Páncreas y Motilidad (HIPAM)-Departamento de Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM), Hospital General de México. Dr. Eduardo Liceaga, Dr. Balmis #148, Col. Doctores C.P. 06726, México Distrito Federal, México.

Tel: +52 5556232673; fax: +52 5556232669; e-mail: maxjulio@prodigy.net.mx

Abstract

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 (CCR5) and activation (CD28) 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 Escherichia coli lipopolysaccharide (LPS), Staphylococcus 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, CCR5 expression in CD4+ α4β7+ cells remained unchanged in IBS, but decreased in controls (= 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 IL8/CXCL8 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.

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