Mycobacterium tuberculosis subverts the differentiation of human monocytes into dendritic cells

Mariotti, Sabrina; Teloni, Raffaela; Iona, Elisabetta; Fattorini, Lanfranco; Giannoni, Federico; Romagnoli, Giulia; Orefici, Graziella; Nisini, Roberto

doi:10.1002/1521-4141(200211)32:11<3050::aid-immu3050>3.0.co;2-k

Cited by 82 publications

(88 citation statements)

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“…Stenger et al (15) infected APCs from healthy subjects with M. tuberculosis and found that, beginning from 24 h postinfection, CD1c level decreased in a multiplicity of infection-dependent manner and undetected totally after 48 h, completely suppressing presentation of Ag to CD1c-restricted T cell line. Studies from Mariotti et al and Gagliardi et al (1,16,17) also indicated that, although M. tuberculosis-infected monocytes could differentiate into mature DCs, expression of CD1c selectively lost. Such DCs could not sufficiently activate allogenic cord blood naive T cells, as indicated by great reduction of proliferation, and lack of IFN-g expression, in turn, could not assist the intracellular bactericidal effects mediated by macrophage.…”

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confidence: 86%

“…It was reported that CD1c downregulation after M. tuberculosis infection of APCs results from reduced mRNA levels (15)(16)(17), which is exactly consistent with one of the mechanisms regulating gene expression by miRNA, that is, through degradation of mRNA poly(A) tail to reduce the stability of target mRNA (18). miRNAs, like other small regulatory RNAs, regulate mRNA stability and protein translation efficiency at posttranscriptional stage and therefore play important roles in regulating gene expression (19).…”

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confidence: 99%

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MiR-381-3p Regulates the Antigen-Presenting Capability of Dendritic Cells and Represses Antituberculosis Cellular Immune Responses by Targeting CD1c

Wen

Zhou

Xiong

et al. 2016

The Journal of Immunology

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Tuberculosis is still the widest spread infectious disease in the world, and more in-depth studies are needed on the interaction between the pathogen and the host. Due to the highest lipid components in Mycobacterium tuberculosis, the CD1 family that specifically presents antigenic lipids plays important roles in the antituberculosis immunity, especially CD1c, which functions as the intracellular Ag inspector at the full intracellular range. However, downregulation of the CD1c mRNA level has been observed in M. tuberculosis-infected cells, which is consistent with the regulatory mechanism of miRNA on gene expression. In this study, through combinatory analysis of previous miRNA transcriptomic assays and bioinformatic predictions by web-based algorithms, miR-381-3p was predicted to bind the 3′-untranslated region of CD1c gene. In vivo expression of miR-381-3p in dendritic cells (DCs) of TB patients is higher than in DCs of healthy individuals, inversely related to CD1c. Suppression of CD1c expression in bacillus Calmette–Guérin (BCG)-infected DCs was accompanied with upregulation of miR-381-3p, whereas inhibition of miR-381-3p could reverse suppression of CD1c expression and promote T cell responses against BCG infection. Further study indicated that miR-381-3p is also one of the mediators of the immune suppressor IL-10. Collectively, these results demonstrated the mechanism that suppression of CD1c by BCG infection is mediated by miR-381-3p. This finding may provide a novel approach to boost immune responses to M. tuberculosis.

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confidence: 86%

mentioning

confidence: 99%

MiR-381-3p Regulates the Antigen-Presenting Capability of Dendritic Cells and Represses Antituberculosis Cellular Immune Responses by Targeting CD1c

Wen

Zhou

Xiong

et al. 2016

The Journal of Immunology

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“…Triggering of TLR2 by mycobacterial polar lipids induces upregulation of CD1a, b and c molecules on the plasma membrane of a small percentage of monocytes [62]. On the contrary, monocytes infected with M. tuberculosis before differentiating into DC fail to express CD1a, b and c molecules [63]. This may represent an important immune evasion mechanism.…”

Section: Multiple Mechanisms Influencing Lipid Antigen Presentationmentioning

confidence: 99%

The cellular and biochemical rules of lipid antigen presentation

2009

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The recognition of both protein and lipid antigens follows similar strategies that rely on different molecular mechanisms. APC present lipid antigens exploiting the same mechanisms implicated in lipid translocation, lipoprotein assembly and lipid degradation. An important issue is how the lipid structure contributes to antigenicity. Lipid hydrophobicity influences the modes of internalization by APC, the trafficking through different membrane compartments, the binding to CD1 molecules and the stability of antigenic complexes. Some glycolipids with large hydrophilic parts require processing of the sugar moieties exerted by lysosomal hydrolases. Finally, extraction of lipids from membranes, their solubilization and loading on CD1 molecules are facilitated by the same lysosomal lipid-binding proteins that are also instrumental in lipid catabolism. More recent investigations reveal how lipid-specific immunity is regulated during infections. In this review we describe the main cellular and biochemical rules of lipid antigen presentation and discuss their implications in anti-microbial and autoimmune responses.Key words: Antigen recognition . CD1 . Lipid antigens . TCR IntroductionMembers of the MHC or CD1 families present protein and lipid antigens to T cells, respectively. CD1 molecules are differentially expressed by a variety of cell types including DC, B cells, monocytes, Langerhans cells, stellate hepatic cells, epithelial cells, microglial cells and keratinocytes. In humans, five genes (CD1A, B, C, D and E) encode CD1 proteins. CD1a, CD1b, CD1c and CD1d molecules reach the plasma membrane and are involved in lipid presentation to T cells, whereas CD1e remains intracellular and is involved in lipid processing. Lipid-specific T cells express a variety of TCR heterodimers, with the exception of invariant NKT (iNKT) cells, a CD1d-restricted population that uses a semi-invariant TCR (invariant Va24-Ja18 and variable Vb11 chains in humans, invariant Va14-Ja18 and variable Vb8.2, Vb7 or Vb2 chains in mice).Proteins become antigenic after a series of events starting with partial degradation by the cellular machinery represented by the proteasome or by proteases located in lysosomes (Ly) and endoplasmic reticulum (ER). This immunological function, commonly known as antigen processing, leads to the generation of peptide fragments that are carried to the proximity of MHC molecules with which they form antigenic complexes. A similar scheme applies to the presentation of lipid antigens. Lipids derived from extracellular routes are internalized or alternatively, self-lipid antigens are synthesized within the APC. These lipids are then transported into the cellular compartments where CD1 molecules traffic and after loading onto CD1, form antigenic complexes.The physicochemical properties of lipids and peptides impose the utilization of different strategies by the APC to digest, transport and load each of these classes of molecules. Antigenicity of lipids is achieved with the participation of extracellular and intracellular li...

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“…Besides the overproduction of IL-10, M. tuberculosis also promotes an environment composed of other immunosuppressive mediators such as TGF-b, Th2 cytokines (e.g., IL-4, IL-5, IL-13), deregulation of inflammatory lipids (e.g., PGE 2 ), overproduction of acute-phase proteins (e.g., a1-acid glycoprotein), and low production of bdefensins, among others (Cooper 2009;Hernandez-Pando et al 2009;Cooper et al 2011;Sundareshan et al 2011). Together, the modulation of these factors may be responsible for a bystander effect that allows M. tuberculosis to subvert the differentiation of monocytes into dendritic cells that are deficient in priming naïve T cells and, instead, contribute to pathogenic dissemination (Mariotti et al 2002;Skold and Behar 2008;Rajashree et al 2009). This premise is in line with the imbalance in the relative proportions of blood-circulating monocytes observed in tuberculosis patients, in which the abundance of the CD14 þ CD16 þ subset is accentuated and shown to have a defective differentiation program toward functional dendritic cells (Vanham et al 1996;Balboa et al 2013).…”

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 tuberculosis subverts the differentiation of human monocytes into dendritic cells

Cited by 82 publications

References 45 publications

MiR-381-3p Regulates the Antigen-Presenting Capability of Dendritic Cells and Represses Antituberculosis Cellular Immune Responses by Targeting CD1c

MiR-381-3p Regulates the Antigen-Presenting Capability of Dendritic Cells and Represses Antituberculosis Cellular Immune Responses by Targeting CD1c

The cellular and biochemical rules of lipid antigen presentation

Manipulation of the Mononuclear Phagocyte System by Mycobacterium tuberculosis

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