<i>Mycobacterium leprae</i>Infection in Monocyte-Derived Dendritic Cells and Its Influence on Antigen-Presenting Function

Hashimoto, Ken; Maeda, Yosuke; Kimura, Hiroaki; Suzuki, Koichi; Masuda, Arata; Matsuoka, Masao; Makino, Masahiko

doi:10.1128/iai.70.9.5167-5176.2002

Cited by 63 publications

(74 citation statements)

References 48 publications

(41 reference statements)

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“…Possible inhibitory molecules present in the cell wall of M. leprae include phenolic glycolipid 1 (PGL-1) (23,24). PGL-1 has been implicated in dampening the allogeneic response caused by M. leprae-infected DCs (18). It has also been implicated in reducing cytokine production in macrophages (25).…”

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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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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“…Usually, M. leprae needs 12-14 d for one division and at least 2-5 y for the manifestation of the disease. In vivo studies using the immunodeficient nude mouse indicate that adaptive immunities play an important role in inhibiting the multiplication of M. leprae, and the activation of both CD4 + T cells and CD8 + T cells is an essential element for controlling M. leprae infection (5,6,35). Although CD4 + T cells chiefly act at the initial phase of infection, the contribution of CD8 + T cells in terms of IFN-g production and killing of mycobacteria-infected host cells is necessary in the chronic phase of the infection (36).…”

Section: Discussionmentioning

confidence: 99%

“…The ability of BCG-infected DCs and macrophages to stimulate T cells was assessed using an autologous APC-T cell coculture as previously described (6,28). Purification of CD4 + and CD8 + T cells was conducted by using negative-isolation kits (Dynabeads 450, Dynal Biotech) (28).…”

Section: Apc Functions Of Dcsmentioning

confidence: 99%

“…Thus, few numbers of bacilli are observed in the lesion of paucibacillary leprosy. The activation of T cells is induced by DCs loaded with bacilli or its component, which display various antigenic molecules on their surface, including the immunodominant Ags (5,6). Previously, we identified major membrane protein (MMP)-II (gene name bfrA or ML 2058) as one of the immunodominant Ags of M. leprae (7).…”

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confidence: 99%

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Enhanced Activation of T Lymphocytes by Urease-Deficient Recombinant Bacillus Calmette-Guérin Producing Heat Shock Protein 70-Major Membrane Protein-II Fusion Protein

Mukai

Maeda

Tamura

et al. 2010

The Journal of Immunology

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To activate naive T cells convincingly using Mycobacterium bovis bacillus Calmette-Guérin (BCG), recombinant BCG (BCG-D70M) that was deficient in urease, expressed with gene encoding the fusion of BCG-derived heat shock protein (HSP) 70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed. BCG-D70M was more potent in activation of both CD4+ and CD8+ subsets of naive T cells than recombinant BCGs including urease-deficient BCG and BCG-70M secreting HSP70–MMP-II fusion protein. BCG-D70M efficiently activated dendritic cells (DCs) to induce cytokine production and phenotypic changes and activated CD4+ T cells even when macrophages were used as APCs. The activation of both subsets of T cells was MHC and CD86 dependent. Pretreatment of DCs with chloroquine inhibited both surface expression of MMP-II on DCs and the activation of T cells by BCG-D70M–infected APCs. The naive CD8+ T cell activation was inhibited by treatment of DCs with brefeldin A and lactacystin so that the T cell was activated by TAP- and proteosome-dependent cytosolic cross-priming pathway. From naive CD8+ T cells, effector T cells producing perforin and memory T cells having migration markers were produced by BCG-D70M stimulation. BCG-D70M primary infection in C57BL/6 mice produced T cells responsive to in vitro secondary stimulation with MMP-II and HSP70 and more efficiently inhibited the multiplication of subsequently challenged M. leprae than vector control BCG. These results indicate that the triple combination of HSP70, MMP-II, and urease depletion may provide a useful tool for inducing better activation of naive T cells.

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“…Supporting the concept that M. tuberculosis modulates its environment and the functional capacity of antigen-presenting cells in its favor, a recent study in zebrafish shows that its close pathogenic relative, Mycobacterium marinum, is able to avoid immune recognition by using cell surface-associated phthiocerol dymycoceroserate (PDIM) lipids, and at the same time, to promote the recruitment of permissive macrophages to site of infection via phenolic glycolipids (PGLs) (Cambier et al 2013). Although the description of this study does not include the modulation of monocytes or dendritic cells by M. marinum, it can be inferred that PGLs may also be responsible for the induction of anti-inflammatory factors that modulate the recruitment of monocytes that differentiate poorly into effective antigen-presenting dendritic cells, as shown recently for M. tuberculosis and M. leprae (Goulart et al 2000;Hashimoto et al 2002).…”

Section: Dendritic Cell Differentiation and Activation: Manipulation mentioning

confidence: 99%

Manipulation of the Mononuclear Phagocyte System by Mycobacterium tuberculosis

Lugo-Villarino

Neyrolles

2014

Cold Spring Harbor Perspectives in Medicine

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Over the past 20 years, there has been an emerging appreciation about the role of the mononuclear phagocyte system (MPS) to control and eradicate pathogens. Likewise, there have been significant advances in dissecting the mechanisms involved in the microbial subversion of MPS cells, mainly affecting their differentiation and effector functions. Mycobacterium tuberculosis is a chronic bacterial pathogen that represents an enigma to the field because of its remarkable ability to thrive in humans. One reason is that M. tuberculosis renders a defective MPS compartment, which is perhaps the most ingenious strategy for survival in the host given the prominence of these cells to modulate microenvironments, their function as sentinels and orchestrators of the immune response, and their pathogenic role as reservoirs for microbial persistence. In this article, the principal strategies used by M. tuberculosis to subvert the MPS compartment are presented along with emerging concepts.

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Mycobacterium lepraeInfection in Monocyte-Derived Dendritic Cells and Its Influence on Antigen-Presenting Function

Abstract: Host defense against Mycobacterium leprae infection is chiefly mediated by gamma interferon (IFN-␥؉ -and CD8 ؉ -T-cell subsets. M. leprae is a unique pathogen which remains resistant to DC-mediated T-cell immunity, at least in the early stages of infection.

Cited by 63 publications

References 48 publications

Mycobacterium leprae Inhibits Dendritic Cell Activation and Maturation

Mycobacterium leprae Inhibits Dendritic Cell Activation and Maturation

Enhanced Activation of T Lymphocytes by Urease-Deficient Recombinant Bacillus Calmette-Guérin Producing Heat Shock Protein 70-Major Membrane Protein-II Fusion Protein

Manipulation of the Mononuclear Phagocyte System by Mycobacterium tuberculosis

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