Authors: Ferrara, G.; Bleck, B.¹; Richeldi, L.²; Reibman, J.¹; Fabbri, L. M.²; Rom, W. N.¹; Condos, R.¹

Source: Scandinavian Journal of Immunology, Volume 68, Number 6, December 2008 , pp. 668-674(7)

Publisher: Wiley-Blackwell

Abstract:

The interaction of Mycobacterium tuberculosis (MTB) with the immune system is mediated by cytokine and chemokine responses of macrophages and/or dendritic cells. Chemokine (C-C motif) ligand 18 (CCL18) and interleukin (IL)-10 are major factors secreted by phagocytes, postulated to recruit naïve T lymphocytes and inhibit pro-inflammatory cells. Our study investigated the role of CCL18 and IL-10 in an in vitro model of infection by MTB in human macrophages. CD14⁺ monocytes, obtained from the peripheral blood of eight healthy donors, differentiated in monocyte-derived macrophages (MDM) with monocyte-colony stimulating factor (100 ng/ml) for 6 days, were stimulated in vitro with lipopolysaccharide (LPS) (1 μg/ml) and with heat killed MTB Hv37Ra (multiplicity of infection 1:5) for 24 h. Alveolar macrophages from five healthy donors were infected with MTB Hv37RA. CCL18 protein and mRNA were detected by enzyme-linked immunosorbent assay (ELISA) and real-time PCR, IL-10 levels by ELISA. Stimulation of MDM with LPS or MTB led to a significant increase in CCL18 protein (control 2.67 ± 0.46 ng/ml, LPS 4.05 ± 0.56 ng/ml, with MTB 6.70 ± 1.59 ng/ml, n = 5, P < 0.05) and specific mRNA levels (control 0.09 ± 0.01, LPS 0.24 ± 0.11, with MTB 0.34 ± 0.08 CCL18/Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), n = 3, P < 0.05). A significant increase of the production of CCL18 was observed in infected alveolar macrophages. IL-10 levels increased from 38.52 ± 26.38 pg/ml in control cells to 1129.32 ± 235.00 and 974.25 ± 164.46 pg/ml in LPS and MTB treated cells, respectively (P < 0.05). Up-regulation of CCL18 and IL-10 in macrophages by MTB may be involved in the recruitment of naïve T cells in association with local suppressive immunity against intracellular pathogens. This could represent a mechanism of tolerance during the early phases of infection.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-3083.2008.02182.x

Affiliations: 1: Bellevue Chest Service, Division of Pulmonary and Critical Care Medicine, NYU School of Medicine, New York, NY, USA 2: Section of Respiratory Diseases, Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy

Publication date: 2008-12-01

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• In this Subject: Microbiology ,  Allergy & Immunology
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