Bacillus Calmette-Gu�rin shares with virulent the capacity to subvert monocyte differentiation into dendritic cell: implication for its efficacy as a vaccine preventing tuberculosis

Gagliardi, Maria Cristina; Teloni, Raffaela; Mariotti, Sabrina; Iona, Elisabetta; Pardini, Manuela; Fattorini, Lanfranco; Orefici, Graziella; Nisini, Roberto

doi:10.1016/j.vaccine.2004.07.009

Cited by 32 publications

(41 citation statements)

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“…Besides macrophages, which are the primary target for infection by mycobacteria (21), dendritic cells (DCs) are pivotal in determining the nature of the antimycobacterial response (15,35,38). Importantly, mycobacteria, including the vaccine strain M. bovis bacillus Calmette-Guérin (BCG), are able to suppress the immune response by interfering with the normal function of DCs (23,73). Induction of the immunosuppressive cytokine interleukin-10 (IL-10) has a negative effect on the production of the proinflammatory cytokine IL-12 and inhibits a Th1-biased response which is necessary for mycobacterial clearance (14,45).…”

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confidence: 99%

Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN

et al. 2009

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The C-type lectin dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is the major receptor on DCs for mycobacteria of the Mycobacterium tuberculosis complex. Recently, we have shown that although the mannose caps of the mycobacterial surface glycolipid lipoarabinomannan (ManLAM) are essential for the binding to DC-SIGN, genetic removal of these caps did not diminish the interaction of whole mycobacteria with DC-SIGN and DCs. Here we investigated the role of the structurally related glycolipids phosphatidylinositol mannosides (PIMs) as possible ligands for DC-SIGN. In a binding assay with both synthetic and natural PIMs, DC-SIGN exhibited a high affinity for hexamannosylated PIM 6 , which contains terminal ␣(132)-linked mannosyl residues identical to the mannose cap on ManLAM, but not for di-and tetramannosylated PIM 2 and PIM 4 , respectively. To determine the role of PIM 6 in the binding of whole mycobacteria to DC-SIGN, a mutant strain of M. bovis bacillus Calmette-Guérin deficient in the production of PIM 6 (⌬pimE) was created, as well as a double knockout deficient in the production of both PIM 6 and the mannose caps on LAM (⌬pimE ⌬capA). Compared to the wild-type strain, both mutant strains bound similarly well to DC-SIGN and DCs. Furthermore, the wild-type and mutant strains induced comparable levels of interleukin-10 and interleukin-12p40 when used to stimulate DCs. Hence, we conclude that, like ManLAM, PIM 6 represents a bona fide DC-SIGN ligand but that other, as-yet-unknown, ligands dominate in the interaction between mycobacteria and DCs.

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confidence: 99%

Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN

et al. 2009

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“…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: 61%

“…In this study, BCG, an attenuated live culture preparation of Mycobacterium bovis, was used to mimic the immune effects induced by virulent strain H37Rv; one of the reasons is that BCG infection also induces downregulated CD1 expression on APCs, further demonstrating the inability of BCG to fully activate anti-TB-protective immunity especially in adults (17). In this study, BCG infection of both differentiating monocytes and differentiated DCs showed significant reduction of CD1c accompanied with the elevated expression of miR-381-3p.…”

Section: Discussionmentioning

confidence: 99%

“…To investigate whether the differential expression of CD1c and miR-381-3p in DCs between TB patients and healthy subjects was due to pathogen infection, we used an in vitro model using BCG to infect monocytes, as described by previous studies (17). We infected the G4-treated monocytes with BCG and detected the expression of CD1c with flow cytometry, as well as CD1c mRNA and miR-381-3p 3 d later by qRT-PCR.…”

Section: Bcg Infection Decreased Cd1c Through Increasing Mir-381-3pmentioning

confidence: 99%

“…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: 96%

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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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Dendritic Cells in Tuberculosis

Schaible¹,

Winau²

2006

Handbook of Dendritic Cells

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Bacillus Calmette-Gu�rin shares with virulent the capacity to subvert monocyte differentiation into dendritic cell: implication for its efficacy as a vaccine preventing tuberculosis

Cited by 32 publications

References 35 publications

Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN

Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN

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

Dendritic Cells in Tuberculosis

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