It is one of the leading causes of maternal, as well as perinatal morbidity and FGFR inhibitor mortality, even in developed countries. Despite intensive research efforts, the aetiology and pathogenesis of pre-eclampsia are not understood completely.

Increasing evidence suggests that an excessive maternal systemic inflammatory response to pregnancy with activation of both the innate and adaptive arms of the immune system is involved in the pathogenesis of the disease [1,2]. We have demonstrated previously that the complement system is activated with increased terminal complex formation in the third trimester of normal human pregnancy, and further in pre-eclampsia, as shown by the elevated amounts of activation markers in the systemic circulation [3]. However, in our recent study, the role of the mannose-binding lectin (MBL)-mediated

lectin pathway has been ruled out in the pathological complement activation observed in pre-eclampsia [4]. Ficolins are pattern recognition molecules of the innate immune system that bind to carbohydrate moieties present on the surface of microbial pathogens, apoptotic and necrotic cells. They act through two distinct routes: by initiating the lectin pathway of complement activation in concert with attached MBL-associated serine proteases (MASPs) and by a primitive opsonophagocytosis [5]. Ficolins are oligomeric proteins consisting of an N-terminal DZNeP cost cysteine-rich region, a collagen-like domain and a C-terminal globular fibrinogen-like domain. The latter is responsible Galeterone for carbohydrate binding [6]. Three types of ficolins have been identified in humans: ficolin-2 (L-ficolin), ficolin-3 (H-ficolin) and ficolin-1 (M-ficolin). The mRNA of ficolin-2 is expressed primarily

in the liver and its protein product is secreted into the blood circulation. Ficolin-2 exhibits lectin activity toward N-acetyl-glucosamine (GlcNAc) and 1, 3-β-D-glucan. Ficolin-3 mRNA is expressed in the liver and lung. In the liver, ficolin-3 is produced by bile duct epithelial cells and hepatocytes, and is secreted into the bile and circulation. In the lung, ficolin-3 is produced by ciliated bronchial epithelial cells and type II alveolar epithelial cells, and is secreted into the bronchus and alveolus. Ficolin-3 binds to GlcNAc, N-acetyl-galactosamine (GalNAc) and fucose. Ficolin-1 mRNA is expressed in monocytes, the lung and spleen. Its protein product has been identified in secretory granules of neutrophils and monocytes, as well as in type II alveolar epithelial cells. Nevertheless, it is present in the circulation at very low levels compared to ficolin-2 and ficolin-3. Ficolin-1 exhibits binding activity towards GlcNAc, GalNAc and sialic acid [7].

While gain of Egr2 caused a decrease in Socs1 mRNA, loss of Egr2 resulted in downregulation of IL-7R, upregulation of Socs1, and inhibition of Stat5 phosphorylation and IL-7-mediated survival post-selection. Therefore, PF-562271 nmr expression of Egr2 following positive selection links the initial TCR signaling event to subsequent survival of signaled cells. Two control points during thymocyte development

govern the number and diversity of mature T cells. The first, β-selection, takes place in CD4−CD8−double-negative (DN) thymocytes 1. Functional rearrangement of the β-chain of the TCR, and its association with the invariant pTα chain to form the preTCR, leads to a proliferative burst and differentiation into CD4+CD8+ double-positive (DP) thymocytes. During this transition, the TCR-α chain rearranges and associates with the β chain to form the mature αβTCR. At the second control point, a selection process operates to ensure that FG-4592 price only those cells

bearing TCR with appropriate affinity for self-peptide-MHC survive. The majority of immature thymocytes bear TCR with no or very low affinity for peptide-MHC, and die by neglect. Thymocytes expressing TCR with very high affinity for peptide-MHC are deleted via negative selection. Those thymocytes whose TCR have intermediate affinity for peptide-MHC receive survival signals and develop into either CD4+ single-positive (CD4SP) helper or CD8+ single-positive (CD8SP) cytotoxic T cells; this process is termed positive selection 2. Positive and negative

Forskolin solubility dmso selection are distinguished by the activation of distinct signaling pathways downstream of the TCR, with Erk1 and 2 essential for positive selection 3, 4, and p38/Jnk and Erk5 mediating negative selection (reviewed in 5). Calcineurin signaling is also necessary for positive selection, activating its own downstream signaling cascade, and being required to establish the threshold for Erk activation during the selection process 6. The early growth response (Egr) transcription factors Egr1 7, Egr2 8 and Egr3 9 are central players throughout the development of T lymphocytes. All three are induced upon activation of the pre-TCR 10–12, and their overexpression can force progression through β-selection 10, 13. Egr1 and Egr3 promote survival at β-selection 14, and Egr3 is also required for the post-β-selection proliferative burst to occur 12. These transcription factors are also induced rapidly following ligation of the αβTCR, both during thymocyte selection 15 and in mature T cells responding to antigen-MHC, where Egr1 has a role in upregulation of IL2 transcription 16, and Egr2 and Egr3 are required for induction of anergy 17, 18, and regulate expression of FasL 19, 20.

These results point to the role of reduced oxygenation to the pathogenesis of inflammatory disorders and/or autoimmune diseases, which are associated with over-expression of some of these receptors [26, 33, 43]. The influence of low pO2 on the expression profile of immune-related surface receptors has been previously documented in other monocytic lineage cells, such as primary monocytes exposed to short-term hypoxia [36] and monocyte-derived mDCs generated under long-term hypoxic Ponatinib conditions [18, 23], and the results reported here extend to iDCs this trend of response to hypoxia. However, different combinations

of receptor-encoding genes are expressed in these cell populations, suggesting that hypoxia may activate a specific transcriptional response in MP depending on their differentiation/maturation stage, which probably represents a mechanism of regulation of the amplitude and duration of inflammatory responses, and the challenge of future studies will be to validate these data in vivo. TREM-1 is one of the few hypoxia-inducible gene targets in H-iDCs shared

with H-mDCs and monocytes. TREM-1 mRNA expression is consistently expressed on H-iDCs generated from different LDE225 in vivo donors but not on the normoxic counterpart, confirming previous evidence of TREM-1 downregulation during monocyte to iDCs differentiation under normoxic conditions [28, 30]. mRNA induction is paralleled by expression of the membrane-bound receptor and its soluble form, detectable in several inflammatory disorders [29, 37, 44]. TREM-1 inducibility by hypoxia is reversible, because cell reoxygenation

results in marked decrease of the receptor supporting the role of low pO2 as a TREM-1 inducer in iDCs. In line with these findings, we provide Exoribonuclease evidence that the HIF/HRE system is implicated, at least in part, in TREM-1 gene inducibility by hypoxia. H-iDCs treatment with echinomycin, a known specific inhibitor of HIF-1 binding to HRE and transcriptional activity [39], downmodulates TREM-1 mRNA and surface protein levels. The potential contribution of other transcription factors, known to mediate hypoxia-dependent gene transactivation in myeloid cells [11, 17, 45], to the regulation of TREM-1 expression in H-iDCs is currently under investigation. These results suggest that TREM-1 expression in iDCs in vivo may vary dynamically with the degree of local tissue oxygenation, which is quite heterogeneous and rapidly fluctuating in diseased tissues [24], giving rise to distinct DC subsets potentially endowed with different functional properties TREM-1 is functionally active in H-iDCs, as demonstrated by the finding that TREM-1 cross-linking by an agonist mAb on H-iDCs increases surface expression of CXCR4 and CD86 and promotes that of CCR7 and CD83, which play a central role in T-cell migration and activation [46].

trachomatis infection. To this point, Vorinostat molecular weight our observations certainly call for further studies on how C. trachomatis may facilitate direct and indirect control of host ligand expressions, as this may be significant in furthering our understanding of the impact of this bacterium on a variety of host cellular immune responses, including cytolytic CD8 T cells and NK cells. The cytolytic CD8 T cell is a key mediator in the control of many intracellular microbial infections. However, the protective role of CD8 T cells against C. trachomatis infection is not clear, as numerous reports based on

mouse models of C. trachomatis infection suggest that CD4 T cells are central to protective immunity against this bacterium. Nevertheless, it has also been shown that adoptive transfer of Chlamydia-specific CD8 T cells to MoPn-infected mice results in the resolution of infection (Igietseme et al., 1994). In vitro, it has also been demonstrated that a Chlamydia-specific-CD8

T cell clone exhibits cytolytic activity against C. trachomatis-infected human epithelial cells in coculture experiments (Kim et al., 1999). Furthermore, differing from mouse models (Su and Caldwell, 1995), a significant CD8 T cell infiltrate is observed in the human endocervix during C. trachomatis infection (Ficarra et al., 2008). If one accepts the MK-2206 concentration possibility that CD8 T cells may play some role in protective immunity against C. trachomatis infections in humans, when viewed from the perspective of the pathogen, our results suggest that SB-3CT decreased MHC expression on infected and

neighboring noninfected cells may be advantageous to chlamydial survival in vivo, widening the time frame for unfettered growth within the infected cell and possibly for spread of the infection. However, from the perspective of the host response to infection, a decrease in MHC expression in conjunction with the increase in MICA expression on infected cells may be, through NK cell-mediated cytolysis, the pathogen’s death knell. While MHC downregulation could be utilized by C. trachomatis to evade host CD4+ and CD+8 T cell responses, MICA upregulation in combination with MHC class I downregulation is associated with enhanced susceptibility of intracellular microorganisms to NK cell activity (Bauer et al., 1999). The role of NK cells in the early response to genital chlamydial infection has been implicated in murine studies that demonstrate that depletion of NK cells results in exacerbation of chlamydial pathogenesis (Tseng & Rank, 1998). Our in vitro data also indicate that C. trachomatis infection renders A2EN endocervical epithelial cells susceptible to NK cell lysis. This finding is similar to observations reported by others (Hook et al., 2004) using infected SiHa cervical epithelial cells and NK cells derived from human peripheral blood mononuclear cells. In this study, we extended Hook et al.

ATP and other nucleotides can induce an array of intercellular signals, depending on the receptor subtype and pathways involved [20]. In damaged tissues, ATP is released in high concentrations, and functions as chemoattractant, generating a broad spectrum of pro-inflammatory responses [21]. ATP can also trigger mycobacterial killing in infected macrophages [22-24], can stimulate

phagosome–lysosome fusion through P2X7 receptor activation [25], and can drive Th-17 cell differentiation in the murine lamina selleck propria [26]. In a study focusing on the novel M. tuberculosis vaccine MVA85A, a drop in extracellular ATP consumption by PBMCs from subjects 2 weeks after vaccination corresponded with a decrease in CD4+CD39+ Treg cells and a concomitant increase in the co-production of IL-17 and IFN-γ by CD4+ T cells [27]. Further hydrolysis of adenosine monophosphate by ecto-5′-nucleotidase (CD73) generates extracellular adenosine

[20], which modulates inflammatory tissue damage, among others by inhibiting T-cell activation and multiple T-cell effector functions through A2A receptor-mediated signaling [28]. BCG, the only currently available vaccine for TB, fails to protect adults adequately and consistently from pulmonary TB [29], and part of this deficiency may be explained by induction of Treg cells by the BCG vaccine [7, 30, 31]. In this study, Pritelivir we have used live BCG to activate CD8+ Treg cells, and demonstrate that these CD8+ T cells express CD39, and co-express the well-known Treg markers CD25, Foxp3, LAG-3, and CCL4. Finally, we describe involvement of CD39 in suppression by CD8+ T cells. We isolated PBMCs from see more healthy human donors and stimulated

these PBMCs with live BCG [8]. Flow cytometric analysis was performed after 6 days (the full gating strategy is shown in Supporting Information Fig. 1, in compliance with the most recent MIATA guidelines [32]). CD39 was expressed on T cells of donors that responded to purified protein derivative (PPD) in vitro, but not on T cells from PPD nonresponsive donors or on unstimulated cell lines (Fig. 1). CD39 and CD25 were co-expressed on both CD4+ and CD8+ T cells from PPD-responsive donors after stimulation with live BCG (Fig. 1). CD8+CD39+ T cells co-expressed the Treg-cell markers CD25, LAG-3, CCL4, and Foxp3 (Fig. 2A). There was no co-expression of CD39 with CD73, consistent with other studies on human Treg cells [33] (data not shown). Gating CD8+ T cells on Foxp3 and LAG-3 [8] demonstrated that the majority of these cells also expressed CD39 as well as CD25 (Fig. 2B). Boolean gating was used to analyze expression of multiple markers on single cells (Fig. 2C). A significantly higher percentage of CD3+CD8+CD4− T cells from PPD responders expressed CD39 as compared with nonresponders (p = 0.03; Mann–Whitney test).

In order to amplify using FR2/LJH primers, in the first PCR 50 ng genomic DNA were used and the reaction mix contained 1× PCR buffer, 200 µM 2′-deoxynucleosides 5′-triphosphate (dNTPs), 2 µM primers, 2 mM MgCl2, 0·001% gelatin and 1·5 U Taq DNA polymerase. The PCR conditions were initial denaturation at 95°C

for 7 min followed by 40 cycles of the following parameters: denaturation, 94°C for 45 s; annealing, 50°C for 30 s; and extension, 72°C for 45 s. For the second round the reaction mixture contained 1 µl of the first PCR product and primers FR2 and VLJH. The cycling protocols to FR3/LJH were the same as FR2, with the exception of the annealing temperature (56°C). To amplify the Fr1c/JH1–6 primers, PLX-4720 solubility dmso we employed the same reaction mix described above without gelatin and

supplemented with 10% dimethylsulphoxide (DMSO), 1·25 U of Taq DNA polymerase and 50 ng of genomic DNA. The PCR conditions were the same as FR2, with the exception Roscovitine ic50 of 35 cycles and annealing temperature of 60°C. Samples in which DNA amplification was not clear were reamplified using the following specific primers: one directed to the FR1 region and the other to the JH region. PCR to amplify the GAPDH gene was performed under standard conditions, with the exception of an annealing temperature of 55°C. The specific primers are indicated in Table 2 and the samples were amplified as described above. Bcl-2/JH translocation was analysed by a modified PCR–enzyme-linked immunosorbent assay (ELISA) technique (PharmaGen, Madrid, Spain), using primers directed to the major breakpoint region (mbr) and minor 3-mercaptopyruvate sulfurtransferase breakpoint region (mcr) of the bcl-2 oncogene coupled with LJH

primer as indicated in Table 2[21]. Briefly, the PCR reactions were performed in similar conditions as described above, using 2′-deoxyuridine 5′-triphosphate (dUTP) digoxygenin instead of thymidine triphosphate (dTTP) and 100 ng of genomic DNA at an annealing temperature of 60°C. The amplified product was hybridized to a biotin-labelled probe and quantified by ELISA, according to the manufacturer’s instructions. The PCR reaction was performed under standard conditions, as described above, under the following amplification conditions: initial denaturation at 95°C for 7 min followed by 30 cycles using the following parameters: denaturation, 94°C for 45 s; annealing, 56°C for 45 s; and extension, 72°C for 110 s. The PCR products were analysed on 3% agarose gels using the FR1c/JH1–6 or FR2/LJH-VLJH amplification protocol or 8% polyacrylamide gels using the FR3/LJH amplification protocol. Gels were photographed under ultraviolet light after staining with ethidium bromide or silver nitrate staining. To determine the sensitivity of our IgH PCR method, we prepared serial 10-fold dilutions of the LM cell line (lymphoblastic lymphoma) in normal peripheral blood mononuclear cells (PBMC). For this purpose, 100–105 clonal B lymphocytes from the LM cell line were diluted with 105 PBMC.

An enhanced skin test response to PPD after TNF-α treatment was associated with a reduction

Tanespimycin purchase in the BCG bacillary loads in the lymph nodes when compared to the BSA-injected guinea pigs (Fig. 1b). In the present study, no viable M. bovis BCG were detected in the spleen of either TNF-α- and BSA-injected guinea pigs 6 weeks after M. bovis BCG infection. This can be explained on the basis of studies by others that a maximum level of viable BCG organisms in spleen was seen 20 days post-vaccination, after which there was a significant decrease in the bacilli in spleen [39]. It is known that in vivo injection of TNF-α increases the resistance of mice to virulent M. tuberculosis or M. avium complex, as it resulted in decreased bacteria in the tissues [16,31]. Conversely, treatment with anti-TNF-α antibody enhanced the susceptibility of mice to tuberculosis [2,13]. In M. marinum-infected zebra fish, loss of TNF-α signalling accelerated bacterial growth and caused increased

mortality, although TNF-α was not required for tuberculous granuloma formation [40]. In vitro studies from our laboratory also support our findings, as rgpTNF-α and rgpIFN-γ, alone or in combination, inhibited the intracellular growth of M. tuberculosis in guinea pig macrophages in vitro[25]. Conversely, alveolar and peritoneal macrophages from Dorsomorphin solubility dmso BCG-vaccinated guinea pigs treated with anti-gpTNF-α antibody in vitro showed increased mycobacterial growth [20]. Furthermore, we reported that injection of anti-TNF antibody into BCG-vaccinated and non-vaccinated guinea pigs

following aerosol challenge with virulent M. tuberculosis resulted in splenomegaly Resveratrol and presence of plasma cells in the granulomas in the BCG-vaccinated guinea pigs, while splenic granulomas were more organized in the non-vaccinated guinea pigs [24]. Thus, anti-TNF-α seems to have a differential effect after M. tuberculosis infection, as large amounts of TNF-α and greater number of bacillary loads occur in non-vaccinated guinea pigs versus lower levels of TNF-α and reduced numbers of bacilli in the vaccinated animals [26,41,42]. In the tuberculous pleurisy model, no necrosis was evident after the anti-TNF-α treatment, while the treatment altered the cellular composition of the pleural effusion, as well as increasing the cell-associated mycobacterial loads in the granulomas [23]. In order to determine whether TNF-α treatment also altered the cytokine mRNA expression after BCG vaccination, lymph node and spleen cells were stimulated in vitro with PPD. TNF-α treatment enhanced the IL-12p40 mRNA expression in both lymph node and spleen cells upon antigen restimulation (Fig. 4a). These results are in agreement with previous reports as well as our in vitro experiments in which rgpTNF-α enhanced both IL-12p40 and IFN-γ mRNA expression [20,21].

, 2001; Bellamy, 2003; Britton et al., 2007), can impact the presentation of tuberculosis pathophysiology. Several studies have reported a relationship between P2X7 polymorphisms and susceptibility to tuberculosis. check details Research conducted by Li et al. (2002) was the first to describe that P2X7 gene polymorphisms were associated with clinical tuberculosis presentation in a Gambian population; however, as discussed

above, conflicting data regarding the role of P2X7 in tuberculosis disease susceptibility and presentation have been reported (Fernando et al., 2007; Niño-Moreno et al., 2007; Mokrousov et al., 2008; Xiao et al., 2009; Sambasivan et al., 2010). Metaanalyses increase the effective sample size under investigation through the pooling of data from individual association studies, thereby enhancing statistical power for assessing the respective genetic effects on disease susceptibility and presentation. The analysis described in this report demonstrated that the 1513 locus alleles were significantly associated with tuberculosis susceptibility in the general population, with estimated ORs of 1.44 (95% CI 1.23–1.68; P<0.00001), corresponding to a relative risk of 1.33, i.e., subjects with the C allele had a 33% higher risk of developing

tuberculosis than those with the A allele. The −762 locus had no statistically significant association with tuberculosis LEE011 mw susceptibility in the population as a whole, with estimated ORs of 1.01 (95% CI 0.70–1.44; P=0.97). This analysis suggested that the protective effects associated with the −762 C allele in the Gambian population (Li et al., 2002) require additional research, further suggesting that polymorphisms in other loci are likely involved with disease susceptibility. From the forest plot of the 1513 C allele (Fig. 1), the ORs and the corresponding

95% CIs in the majority of the studies CHIR-99021 ic50 were almost on the right side of the vertical line (OR=1.0), except for one study (Xiao et al., 2009). Although the weight of this study (Xiao et al., 2009) was heavy (23.25%) in this metaanalysis, the pooled result still indicated a significant association with tuberculosis susceptibility (P<0.00001), suggesting that the 1513 AC polymorphism may actually confer significant tuberculosis susceptibility in populations. On the other hand, the distribution of ORs and CIs about −762 C in different studies varied around the vertical line (OR=1.0) (Fig. 2), suggesting that additional research regarding the association between −762 C and the development of clinical tuberculosis in different populations was still warranted.

16,17 Mice deficient in tumour necrosis factor-α (TNF-α) or lymphotoxins (LTs) reveal profound defects in FDC development.15,18,19 In addition, other cytokines including IL-4 and IL-6 appear to be associated with FDC development.20,21 In this report, we present evidence that IL-15 enhances the proliferation of human FDCs and regulates chemokine secretion of human FDCs. Interleukin-15 is an IL-2-like T-cell proliferation factor that is required for the generation

of cytotoxic T lymphocytes and natural killer cells.22–24 It is also important in humoral immunity.25–27 Interleukin-15 enhances the proliferation and immunoglobulin secretion of human peripheral B cells and is involved in B-cell lymphomagenesis.28–34 The heterotrimeric IL-15 receptor (IL-15R) specifically binds IL-15. The IL-15 receptor α-chain (IL-15Rα) is the distinctive component for this Smoothened antagonist specific binding, whereas the IL-15 receptor β-chain (IL-2Rβ)

and IL-15 receptor γ-chain (IL-2γ) chains in the receptor complex, which are shared with find more the IL-2 receptor, are involved in signal transduction.35 Unlike IL-2, however, IL-15 is expressed in various cell types including dendritic cells, keratinocytes,36 monocytes,37,38 thymic epithelial stromal cells,39 bone marrow stromal cells40 and fibroblasts.41 The membrane-bound form of IL-15 plays an essential role in proliferation, or apoptosis of various kinds of cells in an autocrine fashion.37,42–44 Previously, we showed that IL-15 is produced by human FDCs and presented on the surface in a membrane-bound form.13 The IL-15 enhances U0126 nmr GC-B-cell proliferation rather than protecting GC-B cells from apoptosis. Furthermore, the level of IL-15 on the surface of FDCs increased following the cellular interaction with GC-B cells. However, the functional role of IL-15 in FDCs has not been investigated. In this study, we show that IL-15 augments the proliferation of human primary FDCs in vitro. The FDCs express the IL-15R complex that is functional

because anti-IL-15 or anti-IL-15R antibodies that block IL-15 signalling reduced FDC proliferation. In addition, blocking of FDC IL-15 signalling reduced FDC secretion of CCL-2, CCL-5, CXCL-5 and CXCL-8, suggesting potentially important roles for recruitment of other cellular components required for GC reaction. Because IL-15 is expressed by FDCs within the GC microenvironment and enhances the proliferation of both GC-B cells and FDCs, IL-15 may contribute to the rapid expansion and formation of the GC structure, suggesting an important role of IL-15 in the humoral immune response. Anti-IL-15 monoclonal antibodies (mAbs) [M110, M111 and M112: immunoglobulin G1 (IgG1)] were kindly provided by Dr R. Armitage (Amgen Inc., Seattle, WA). Anti-IL-2Rβ (Mik-β2) was purchased from BD Biosciences, (San Jose, CA). Mouse IgG1 (MOPC 21; used as an isotype control) was purchased from Sigma (St Louis, MO).

They suggested that immunotherapy using autologous MDDC pulsed with lipopeptides was safe, but was unable to generate sustained responses or alter the outcome of the infection. Alternative dosing regimens or vaccination routes may need to be considered to achieve therapeutic benefit.33 During the last decade, DC have been regarded as promising tools for the development of more effective therapeutic vaccines in cancer patients. For patients with late-stage disease, strategies

that combine novel highly immunogenic DC-based vaccines and immunomodulatory antibodies may have a significant effect on enhancing therapeutic immunity by simultaneously enhancing the potency of beneficial immune arms and offsetting immunoregulatory pathways. These optimized therapeutic modalities include the following. Glucopyranosyl lipid A (GLA) is a new synthetic non-toxic analogue of lipopolysaccharide. Pantel et al.127 Osimertinib nmr studied DC directly from vaccinated mice. Within 4 hr,

GLA caused DC to up-regulate CD86 and CD40 and produce cytokines including IL-12p70 in vivo. Importantly, DC removed from mice 4 hr after vaccination became immunogenic, capable of inducing T-cell immunity upon injection into naive mice. These data indicate that a synthetic and clinically feasible TLR4 agonist rapidly stimulates full maturation of DCs in vivo, allowing for adaptive immunity to develop many weeks to months later. Relative to several other TLR agonists, Longhi et al.128 Midostaurin cost found polyinosinic : polycytidylic acid (poly I:C) to be the most effective adjuvant for Th1 CD4+

T-cell responses to a DC-targeted HIV gag protein vaccine in mice. Spranger et al.129 described a new method for preparation of human DCs that secrete bioactive IL-12p70 using synthetic immunostimulatory Resveratrol compounds as TLR7/8 agonists R848 or CL075. Maturation mixtures included the TLR7/8 agonists, combined with the TLR3 agonist poly I:C, yielded 3 days mature DC that secreted high levels of IL-12p70, showed strong chemotaxis to CCR7 ligands, and had a positive co-stimulatory potential. They also had excellent capacity to activate natural killer cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and to induce T-cell-mediated cytotoxic function. Thereby, mature DCs prepared within 3 days using such maturation mixtures displayed optimal functions required for vaccine development. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express TLR9 (including human PDCs and B cells) to mount an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. When used as vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. Preclinical studies indicate that CpG ODNs improve the activity of vaccines targeting infectious diseases and cancer.