<i>Mycobacterium bovis</i>Bacillus Calmette-Guérin infects DC-SIGN– dendritic cell and causes the inhibition of IL-12 and the enhancement of IL-10 production

Gagliardi, Maria Cristina; Teloni, Raffaela; Giannoni, Federico; Pardini, Manuela; Sargentini, Valeria; Brunori, Lara; Fattorini, Lanfranco; Nisini, Roberto

doi:10.1189/jlb.0105037

Cited by 56 publications

(47 citation statements)

References 44 publications

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“…Furthermore, both these viruses also actively suppress type I IFN responses in DC, thereby effectively removing a critical first line of defense in the infected host (11,32). Some mycobacteria suppress DC function by manipulation of signaling via a variety of TLRs and at least one C-type lectin, DC-SIGN (33,34). However, we are unaware of previous reports demonstrating the exact pattern of aberrant activation of DC that we describe in this paper.…”

Section: Discussioncontrasting

confidence: 46%

Francisella tularensis Induces Aberrant Activation of Pulmonary Dendritic Cells

Bosio¹,

Dow

2005

The Journal of Immunology

163

216

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Francisella tularensis is an obligate intracellular bacterium that induces severe, acute, often fatal disease when acquired by the respiratory route. Despite the seriousness of this pathogen, very little is understood about its interaction with key target cells in the airways and lungs (alveolar macrophages and airway dendritic cells (DC)) after inhalation. In this study we demonstrate replication of F. tularensis in primary DC. Early after infection, F. tularensis induced increased expression of MHC class II and CD86 on DC, but not macrophages. This was followed by depletion of DC from the airways and lungs. Despite logarithmic replication and phenotypic maturation of DC, F. tularensis failed to induce production of several key proinflammatory cytokines, including TNF-α and IL-6, from DC. However, F. tularensis infection did elicit production of the potent immunosuppressive cytokine, TGF-β. Furthermore, F. tularensis actively suppressed the ability of DC to secrete cytokines in response to specific TLR agonists. Finally, we also found that infection of DC and macrophages in the lungs appears to actually increase the severity of pulmonary infection with F. tularensis. For example, depletion of airway DC and alveolar macrophages before infection resulted in significantly prolonged survival times. Together, these data suggest F. tularensis is able to selectively uncouple Ag-presenting functions from proinflammatory cytokine secretion by critical APCs in the lungs, which may serve to create a relatively immunosuppressive environment favorable to replication and dissemination of the organism.

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Section: Discussioncontrasting

confidence: 46%

Francisella tularensis Induces Aberrant Activation of Pulmonary Dendritic Cells

Bosio¹,

Dow

2005

The Journal of Immunology

163

216

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“…We detected no bioactive IL-12p70 production in mouse or human cocultures in response to BCG. The inhibition of IL-12p70 production in DC by BCG infection has been reported [19,41]. Alternatively, IL-12p40 may have associated with p19 to produce IL-23 [42].…”

Section: Discussionmentioning

confidence: 99%

“…In human cells, coculture of DC with BCG-infected neutrophils strongly decreased IL-10 production. Mycobacteria trigger IL-10 production by human DC either through direct binding to DC-SIGN [18], or by DC-SIGNindependent signals [19]. In both cases, the inhibitory effects of IL-10 would antagonize the T cell protective response.…”

Section: Discussionmentioning

confidence: 99%

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Mycobacterium bovis BCG‐infected neutrophils and dendritic cells cooperate to induce specific T cell responses in humans and mice

et al. 2008

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Neutrophils are increasingly thought to modulate dendritic cell (DC) functions. We investigated the role of the neutrophil-DC partnership in the response to Mycobacterium bovis BCG-the vaccine used against tuberculosis. We compared neutrophil-DC crosstalk in humans and mice, searching for functional differences. In both species, neutrophils captured fluorescent BCG-enhanced green fluorescent protein (EGFP) and were more phagocytic than DC. Non-apoptotic BCG-infected neutrophils clustered with immature DC, establishing intimate contacts with dendrites, at which fluorescent intact bacilli were observed. Physical interactions between neutrophils and DC were required for DC activation. Human BCG-infected DC produced interleukin (IL)-10, an inhibitory cytokine, whereas DC exposed to BCG-infected neutrophils produced low to undetectable amounts of the cytokine. Mouse BCG-infected neutrophils induced sustained IL-2 production by DC. Human DC exposed to BCG-infected neutrophils stimulated recall T cell reactivity from vaccinated donors. Mouse DC infected with recombinant ovalbumin (OVA)-producing BCG (rBCG ova ) elicited proliferation of TCR-OVA-transgenic CD4 and CD8 T cells. Moreover, exposing DC to rBCG ova -infected neutrophils enhanced OVA presentation. Thus, in mice and humans, neutrophils help DC to cross-present BCG antigens to T cells. Our results suggest that this "mØnage à trois" involving neutrophils, DC and T cells plays a major role in the immune response to BCG.

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“…BCG causes a local inflammation and an influx of mononuclear cells into the bladder wall (8). BCG induces maturation and activation of DCs with interaction with TLRs 2 and 9 and with Dectin-1 (17,19,24,25,26,27) that are important components of the innate immune response. In our patients, mDCs were found in urine after BCG therapy, particularly at the third instillation that corresponds to blood DCs increase.…”

Section: Figurementioning

confidence: 99%

Dendritic cells in blood and urine samples from bladder cancer patients undergoing BCG immunotherapy

Rossi¹,

Lichtner²,

Iori

et al. 2013

Arch Ital Urol Androl

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Objectives: Immunotherapy with BCG (Bacille Calmette-Guérin) after transurethral resection of the bladder tumor represents a highly effective primary treatment for intermediate and high-risk superficial bladder cancer. The effectiveness of this therapy has been documented, but its mechanism of action is not clear yet. In the present study, we investigated the changes of dendritic cells (DC) numbers in peripheral blood and urine of patients with superficial bladder cancer undergoing BCG intravescical therapy Material and method: We have enumerated plasmacytoid and myeloid DCs in the peripheral blood and in the urine of patients with bladder cancer in order to clarify the role of these cells in the evolution of the disease and the effect of therapy. DCs in blood and urine samples were assessed using the single-platform TruCOUNT assay with monoclonal antibodies. The study population included 37 healthy donors and 13 patients with diagnosis of primitive superficial bladder cancer. Results: At the time of diagnosis a reduction of blood DCs was found in patients as opposed to healthy donors, while DCs were not found in the urine in the same way as in healthy subjects. Six of these patients were followed before and after weekly and monthly instillations of BCG. In the peripheral blood, we observed an immunological recovery of DCs from the third weekly instillation up to the sixth. In the urine of patients, we didn't find mDCs or pDCs at T0, but we found a statistically significant change from the third instillation up to the sixth. On the contrary, we didn't find mDCs in urine during monthly instillation. Conclusions: DC Count could be used in the monitoring of patients undergoing BCG therapy. Immunological restoration of mDC numbers in peripheral blood and the efflux in urine could be important for confirming the effectiveness of BCG instillation.

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Mycobacterium bovisBacillus Calmette-Guérin infects DC-SIGN– dendritic cell and causes the inhibition of IL-12 and the enhancement of IL-10 production

Cited by 56 publications

References 44 publications

Francisella tularensis Induces Aberrant Activation of Pulmonary Dendritic Cells

Francisella tularensis Induces Aberrant Activation of Pulmonary Dendritic Cells

Mycobacterium bovis BCG‐infected neutrophils and dendritic cells cooperate to induce specific T cell responses in humans and mice

Dendritic cells in blood and urine samples from bladder cancer patients undergoing BCG immunotherapy

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