DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect?

Soilleux, Elizabeth; En, Sarno; Hernandez, MO; Moseley, E; Horsley, Jo; Lopes, UG; Goddard, Martin; Vowler, SL; Shattock, RJ; Sampaio, E. P.

doi:10.1002/path.1972

Cited by 30 publications

(28 citation statements)

References 25 publications

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“…M. leprae have also been reported inside epidermal cells analysed by TEM (42,46) with bacteria inside a keratinocyte of the epidermis in a leproma.The expression of CD209 (DC sign) triggers the initial contact between DC and T cells by binding to ICAM-3 on T cells (47). It has been suggested that CD209, when induced on macrophages in multibacillary leprosy, contributes to the entry of mycobacteria into these cells(48). Our data show that only a few keratinocytes express CD209.…”

contrasting

confidence: 38%

Interaction of Mycobacterium leprae with the HaCaT human keratinocyte cell line: new frontiers in the cellular immunology of leprosy

Lyrio

Campos-Souza

Corrêa

et al. 2015

Experimental Dermatology

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Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae affecting the skin and peripheral nerves. Despite M. leprae invasion of the skin and keratinocytes importance in innate immunity, the interaction of these cells in vitro during M. leprae infection is poorly understood. Conventional and fluorescence optical microscopy, transmission electronic microscopy, flow cytometry and ELISA were used to study the in vitro interaction of M. leprae with the HaCaT human keratinocyte cell line. Keratinocytes uptake of M. leprae is described, and modulation of the surface expression of CD80 and CD209, cathelicidin expression and TNF-α and IL-1β production of human keratinocytes are compared with dendritic cells and macrophages during M. leprae interaction. This study demonstrated that M. leprae interaction with human keratinocytes enhanced expression of cathelicidin and greatly increased TNF-α production. The highest spontaneous expression of cathelicidin was by dendritic cells which are less susceptible to M. leprae infection. In contrast, keratinocytes displayed low spontaneous cathelicidin expression and were more susceptible to M. leprae infection than dendritic cells. The results show, for the first time, an active role for keratinocytes during infection by irradiated whole cells of M. leprae and the effect of vitamin D on this process. They also suggest that therapies which target cathelicidin modulation may provide novel approaches for treatment of leprosy.

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contrasting

confidence: 38%

Interaction of Mycobacterium leprae with the HaCaT human keratinocyte cell line: new frontiers in the cellular immunology of leprosy

Lyrio

Campos-Souza

Corrêa

et al. 2015

Experimental Dermatology

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“…Man-LAM has also been shown to bind the DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin on DC and macrophages (32), and to interfere with TLR-mediated DC maturation (33). Interestingly, increased DC-SIGN expression in M. leprae-infected DCs has been recently described in L-lep vs T-lep patients (34). This report and a second one (35) showed that DC-SIGN acts as an entry receptor for M. leprae, much the same as has been described for M. tuberculosis (32,36).…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium leprae Inhibits Dendritic Cell Activation and Maturation

Murray¹,

Siddiqui

Mendillo

et al. 2007

The Journal of Immunology

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Leprosy presents with a clinical spectrum of skin lesions that span from strong Th1-mediated cellular immunity and control of bacillary growth at one pole to poor Ag-specific T cell immunity with extensive bacillary load and Th2 cytokine-expressing lesions at the other. To understand how the immune response to Mycobacterium leprae is regulated, human dendritic cells (DC), potent inducers of adaptive immune responses, exposed to M. leprae, Mycobacterium tuberculosis (Mtb), and Mycobacterium bovis bacillus Calmette-Guerin (BCG) were studied for their ability to be activated and to prime T cell proliferation. In contrast with Mtb and BCG, M. leprae did not induce DC activation/maturation as measured by the expression of selected surface markers and proinflammatory cytokine production. In MLR, T cells did not proliferate in response to M. leprae-stimulated DC. Interestingly, M. leprae-exposed MLR cells secreted increased Th2 cytokines as well as similar Th1 cytokine levels as compared with Mtb- and BCG-exposed cells. Gene expression analysis revealed a reduction in levels of mRNA of DC activation and maturation markers following exposure to M. leprae. Our data suggest that M. leprae does not induce and probably suppresses in vitro DC maturation/activation, whereas Mtb and BCG are stimulatory.

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“…Our results indicate that CD209 expression on Schwann cells is involved in the binding to M. leprae. Based on previous studies, it is likely that CD209 is interacting with Man-LAM (i.e., mannose-capped lipoarabinomannan) present in the M. leprae cell wall (9,30). In addition to recognizing mycobacteria, CD209 recognizes HIV and may contribute to AIDS pathogenesis, including HIV infection of peripheral nerve Schwann cells (13,31).…”

Section: Discussionmentioning

confidence: 99%

“…Among these is the C-type lectin receptor, CD209, also known as DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin), which mediates recognition of several pathogens, including viruses, fungi, and bacteria (8). CD209 facilitates cell binding to several species of mycobacteria, including M. tuberculosis, M. bovis, and M. leprae (9,20,30). The recognition of mycobacteria by CD209 has been shown to be mediated by interaction with the mycobacterial mannose-capped lipoarabinomannan (Man-LAM) (9).…”

mentioning

confidence: 99%

Interleukin-4 Regulates the Expression of CD209 and Subsequent Uptake ofMycobacterium lepraeby Schwann Cells in Human Leprosy

et al. 2010

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The ability of microbial pathogens to target specific cell types is a key aspect of the pathogenesis of infectious disease. Mycobacterium leprae, by infecting Schwann cells, contributes to nerve injury in patients with leprosy. Here, we investigated mechanisms of host-pathogen interaction in the peripheral nerve lesions of leprosy. We found that the expression of the C-type lectin, CD209, known to be expressed on tissue macrophages and to mediate the uptake of M. leprae, was present on Schwann cells, colocalizing with the Schwann cell marker, CNPase (2,3-cyclic nucleotide 3-phosphodiesterase), along with the M. leprae antigen PGL-1 in the peripheral nerve biopsy specimens. In vitro, human CD209-positive Schwann cells, both from primary cultures and a long-term line, have a higher binding of M. leprae compared to CD209-negative Schwann cells. Interleukin-4, known to be expressed in skin lesions from multibacillary patients, increased CD209 expression on human Schwann cells and subsequent Schwann cell binding to M. leprae, whereas Th1 cytokines did not induce CD209 expression on these cells. Therefore, the regulated expression of CD209 represents a common mechanism by which Schwann cells and macrophages bind and take up M. leprae, contributing to the pathogenesis of leprosy.The interaction between a microbial pathogen and distinct host cells is a crucial step in the initiation of the immune response and also contributes to the pathogenesis of the disease. In the human disease leprosy, the pathogen Mycobacterium leprae infects at least two cell types, macrophages and Schwann cells, both contributing to disease pathogenesis. The mechanism of Schwann cell infection includes interaction of M. leprae-specific phenolic glycolipid 1 (PGL-1) with laminin 2 in Schwann cell basal lamina and also with the ERBB2 receptor on the cell surface of Schwann cells (36). Infection of Schwann cells by M. leprae contributes to inflammation in leprosy, involving antigen presentation and Toll-like receptor (TLR)-mediated cytokine release (24, 32). The uptake of M. leprae by Schwann cells results in demyelination and subsequent nerve damage in leprosy, a major cause of patient morbidity (35).In contrast to the receptors that mediate uptake of M. leprae by Schwann cells, macrophages use a distinct set of cell surface receptors to facilitate phagocytosis. Among these is the C-type lectin receptor, CD209, also known as DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin), which mediates recognition of several pathogens, including viruses, fungi, and bacteria (8). CD209 facilitates cell binding to several species of mycobacteria, including M. tuberculosis, M. bovis, and M. leprae (9,20,30). The recognition of mycobacteria by CD209 has been shown to be mediated by interaction with the mycobacterial mannose-capped lipoarabinomannan (Man-LAM) (9). Although originally identified on in vitro-derived dendritic cells (DCs), CD209 is expressed by macrophages in leprosy lesions and was shown to be required for optim...

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DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect?

Cited by 30 publications

References 25 publications

Interaction of Mycobacterium leprae with the HaCaT human keratinocyte cell line: new frontiers in the cellular immunology of leprosy

Interaction of Mycobacterium leprae with the HaCaT human keratinocyte cell line: new frontiers in the cellular immunology of leprosy

Mycobacterium leprae Inhibits Dendritic Cell Activation and Maturation

Interleukin-4 Regulates the Expression of CD209 and Subsequent Uptake ofMycobacterium lepraeby Schwann Cells in Human Leprosy

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