Interplay of pathogens, cytokines and other stress signals in the regulation of dendritic cell function

Sabatté, Juan; Maggíni, Julian; Nahmod, Karen; Amaral, María Marta; Martínez, Diego; Salamone, Gabriela; Ceballos, Ana; Giordano, Mirta; Vermeulen, Mónica; Geffner, Jorge

doi:10.1016/j.cytogfr.2007.01.002

Cited by 54 publications

(46 citation statements)

References 158 publications

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“…5 Previously it was demonstrated that CysLTs are able to induce the phagocytosis of opsonized bacteria through the Fcc receptors. 52 Here, we showed that LTC 4 induces the phagocytosis of Zy and also stimulates Dextran and HRP endocytosis by immature DCs.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 In peripheral tissues, immature DCs sense the microenvironment and after their encounter with inflammatory stimuli or pathogens, DCs are activated; a process that is accompanied by several physiological changes and that ends with the maturation of DCs. [3][4][5] Once initiated the process of DCs maturation, the expression of CD80, CD86 and MHC class II molecules increases. [1][2][3][4] The DCs migrate to the draining lymph nodes, as a result of the up-regulation of CCR7, which renders them responsive to CCL19 and CCL21 chemokines that direct their migration to the T-cell areas of lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

“…The maturational status can be modulated by different stimuli. 5 The impact of microbial products through Toll-like receptor leads to DCs that produce interleukin-12 (IL-12)/IL-23 and prime T helper type 1 (Th1)/Th17 responses. 7,8 In contrast, in the absence of inflammatory signals, 'semi-mature' DCs produce IL-10, which primes a regulatory T-cell response.…”

Section: Introductionmentioning

confidence: 99%

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Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Álvarez¹,

Amaral²,

Langellotti³

et al. 2011

Immunology

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Summary Leukotriene C4 is an important mediator in the development of inflammatory reactions and ischaemia. Previous studies have shown that leukotriene C4 is able to modulate the function of dendritic cells (DCs) and induce their chemotaxis from skin to lymph node. In this study, we decided to evaluate the modulation exerted by leukotriene C4 on DCs, depending on their status of activation. We showed for the first time that leukotriene C4 stimulates endocytosis both in immature and lipopolysaccharide (LPS) ‐activated DCs. Moreover, it suppressed the interleukin‐12p70 (IL‐12p70) release, but induces the secretion of IL‐23 by DCs activated with LPS and promotes the expansion of T helper type 17 (Th17) lymphocytes. Furthermore, blocking the release of IL‐23 reduced the percentages of CD4+ T cells producing IL‐17 in a mixed lymphocyte reaction. Ours results suggest that leukotriene C4 interferes with the complete maturation of inflammatory DCs in terms of phenotype and antigen uptake, while favouring the release of IL‐23, the main cytokine involved in the maintenance of the Th17 profile.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Álvarez¹,

Amaral²,

Langellotti³

et al. 2011

Immunology

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“…Therefore, by the addition of specific cytokines or adjuvants, it seems possible to guide the immune response into any desired direction. 54,55 This would allow for further optimize vaccination strategies by protein vaccines against various pathogens.…”

Section: Human Cytomegalovirus Protein Pp65 N Scheller Et Almentioning

confidence: 99%

Human cytomegalovirus protein pp65: an efficient protein carrier system into human dendritic cells

et al. 2007

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Protein-based immunogens are usually poor inducers of CD8 + T cells. To enhance the induction of CD8 + T cells, one approach is the use of protein immunogens coupled to protein transduction domains (PTDs). These are small cationic peptide sequences that significantly enhance the uptake of fused proteins into dendritic cells (DC) and then mediate their presentation in the context of major histocompatibility complex class I (MHC-I) and MHC-II molecules. One drawback of this system is the high concentrations of PTD-fusion proteins required. Here, we show that proteins fused to the human cytomegalovirus tegument protein pp65were bound with higher efficiency to DCs than those fused to the described PTDs TatPTD and Penetratin. Furthermore, the fusion of pp65 to proteins led to an enhanced uptake of these proteins by DCs. Once taken up, CD4 + and CD8 + memory T cells were strongly stimulated ex vivo demonstrating that pp65 was efficiently processed and presented in the context of both MHC-I and MHC-II. These data make pp65 a promising delivery system to induce cellular immune responses by fused protein vaccines.

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“…4A, B) were detected in cultured PBMC from seven donors at significant levels (p < 0.5, in a Wilcoxon signed rank test). These factors are known to modulate the immune response (Sabatte et al 2007). IL-1Ra, the antagonist of the pro-inflammatory cytokine IL-1β and chemotactic factor IP-10 were also increased in most of the donors tested (Fig.…”

Section: Several Cytokines and Chemokines Are Present In Supernatantsmentioning

confidence: 99%

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

Gandini

Reis

Torrentes-Carvalho

et al. 2011

Mem. Inst. Oswaldo Cruz

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Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocytederived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF)-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.Key words: cytokines -dendritic cells -dengue virus -yellow fever vaccine -flavivirus dendritic cell activation by flavivirus • Mariana Gandini et al.

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Interplay of pathogens, cytokines and other stress signals in the regulation of dendritic cell function

Cited by 54 publications

References 158 publications

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Human cytomegalovirus protein pp65: an efficient protein carrier system into human dendritic cells

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

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