DC-SIGN Induction in Alveolar Macrophages Defines Privileged Target Host Cells for Mycobacteria in Patients with Tuberculosis
Open Access
- 15 November 2005
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Medicine
- Vol. 2 (12), e381
- https://doi.org/10.1371/journal.pmed.0020381
Abstract
Interplays between Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) in human and host professional phagocytes, namely macrophages (Mϕs) and dendritic cells (DCs), are central to immune protection against TB and to TB pathogenesis. We and others have recently shown that the C-type lectin dendritic cell–specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN; CD209) mediates important interactions between mycobacteria and human monocyte-derived DCs (MoDCs) in vitro. In order to explore the possible role of DC-SIGN in M. tuberculosis infection in vivo, we have analysed DC-SIGN expression in broncho-alveolar lavage (BAL) cells from patients with TB (n = 40) or with other non-mycobacterial lung pathologies, namely asthma (n = 14) and sarcoidosis (n = 11), as well as from control individuals (n = 9). We show that in patients with TB, up to 70% of alveolar Mϕs express DC-SIGN. By contrast, the lectin is barely detected in alveolar Mϕs from all other individuals. Flow cytometry, RT-PCR, and enzyme-linked immunosorbent assay analyses of BAL-derived fluids and cells indicated that M. tuberculosis infection induces DC-SIGN expression in alveolar Mϕs by a mechanism that is independent of Toll-like receptor-4, interleukin (IL)-4, and IL-13. This mechanism most likely relies on the secretion of soluble host and/or mycobacterial factors that have yet to be identified, as both infected and uninfected bystander Mϕs were found to express DC-SIGN in the presence of M. tuberculosis. Immunohistochemical examination of lung biopsy samples from patients with TB showed that the bacilli concentrate in pulmonary regions enriched in DC-SIGN-expressing alveolar Mϕs in vivo. Ex vivo binding and inhibition of binding experiments further revealed that DC-SIGN–expressing alveolar Mϕs constitute preferential target cells for M. tuberculosis, as compared to their DC-SIGN− counterparts. In contrast with what has been reported previously in MoDCs in vitro, ex vivo DC-SIGN ligation by mycobacterial products failed to induce IL-10 secretion by alveolar Mϕs, and IL-10 was not detected in BALs from patients with TB. Altogether, our results provide further evidence for an important role of DC-SIGN during TB in humans. DC-SIGN induction in alveolar Mϕs may have important consequences on lung colonization by the tubercle bacillus, and on pulmonary inflammatory and immune responses in the infected host.Keywords
This publication has 36 references indexed in Scilit:
- Deciphering the molecular bases ofMycobacterium tuberculosisbinding to the lectin DC-SIGN reveals an underestimated complexityBiochemical Journal, 2005
- How C-type lectins detect pathogensCellular Microbiology, 2005
- DC-SIGN promotes exogenous MHC-I–restricted HIV-1 antigen presentationBlood, 2004
- The Cell Surface Receptor DC-SIGN Discriminates betweenMycobacterium Species through Selective Recognition of the Mannose Caps on LipoarabinomannanJournal of Biological Chemistry, 2003
- DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic CellsThe Journal of Experimental Medicine, 2002
- Mycobacteria Target DC-SIGN to Suppress Dendritic Cell FunctionThe Journal of Experimental Medicine, 2002
- Immunology of TuberculosisAnnual Review of Immunology, 2001
- Mycobacterial surface moieties are released from infected macrophages by a constitutive exocytic eventEuropean Journal of Cell Biology, 2001
- Type 1/Type 2 Immunity in Infectious DiseasesClinical Infectious Diseases, 2001
- ATS/ERS/WASOG statement on sarcoidosisEuropean Respiratory Journal, 1999