This study showed that caregiver protective behavior, which functions to prevent a child from interacting with a novel stimulus, is an important mechanism to consider when understanding toddler stress responses during novel contexts. “
“Memory based on a one-time experience is an important element of its definition as “episodic.” Infants’

memories for one-time experiences over long delays are largely unexplored. Using elicited imitation, we tested 20- and 16-month-olds’ (Experiment 1) and 13-month-olds’ (Experiment 2) memories as a function of number of experiences and delay. Over 1 month, 20- and 16-month-olds remembered individual actions of one-time events; 20-month-olds also remembered temporal order; with verbal reminders, 16-month-olds did as well. Over GPCR Compound Library solubility dmso 3 months, recall depended on multiple experiences. Thirteen-month-olds’ required multiple experiences,

even over 1 month. The findings speak to the gradual emergence of an important element of episodic memory, namely the ability to preserve memories of one-time experiences Y27632 over long periods of time. “
“Toward the end of their first year of life, infants’ overly specified word representations are thought to give way to more abstract ones, which helps them to better cope with variation not relevant to word identity (e.g., voice and affect). This developmental change may help infants process the ambient language more efficiently, thus enabling rapid gains in vocabulary growth. One particular kind of variability that infants must

accommodate is that of dialectal accent, because most children will encounter speakers from different regions and backgrounds. In this study, we explored developmental changes in infants’ ability to recognize words in continuous speech by familiarizing them with words spoken by a speaker of their own region (North Midland-American English) or a different region (Southern Ontario Canadian English), and testing them with passages spoken by a speaker of the opposite dialectal accent. Our results demonstrate that 12- but not 9-month-olds readily recognize words in the face of dialectal variation. Regionally driven dialectal differences produce phonetic variation that straddles the boundary between linguistically relevant and linguistically irrelevant variation. Even for mutually comprehensible Aspartate dialectal accents, such as North Midland-American and Southern Ontario Canadian English, phonetic differences affect the realization of contrasts, which may complicate word recognition. As a result of the Canadian shift, both /ae/ and /I/ are lowered and more backed in Southern Ontario Canadian English, compared with North Midland-American English (Labov, Ash, & Boberg, 2006). For example, [ma:p] may be perceived as “map” in this Canadian dialect, but as “mop” in this American dialect. This may fetter perception for American listeners unfamiliar with the variation introduced by this dialect (e.g., Kraljic, Samuel, & Brennan, 2008).

Moreover, emerging evidence supports a direct correlation between DC numbers and the proliferation rate of peripheral Treg. Thus, Fms-like tyrosine kinase 3 ligand (Flt3L) treatment, which results in the in vivo expansion of classical DC (cDC) 11 leads to a concomitant increase in peripheral Treg 12, 13. Furthermore, it was recently demonstrated that the conditional ablation of cDC from otherwise intact animals results in reduced numbers and impaired homeostatic proliferation of peripheral Treg 13. Here, we readdressed the

role of cDC in the maintenance of peripheral Treg focusing on the role of CD80/86 costimulation. Using constitutive and conditional cDC ablation strategies, we established that peripheral Treg maintenance critically

depends on the presence of cDC expressing CD80/86. Surprisingly however and defying earlier notions 13, 14, the reduction of Treg in animals selleck chemical lacking cDC as such was not inherently associated with lymphocyte activation. Rather than resulting from a tolerance check details failure, the autoinflammatory signatures reported for cDC-deficient mice are thus a consequence of the nonmalignant myeloproliferative disorder these animals develop. We and others recently reported that animals that constitutively lack cDC (CD11c-DTA mice) display normal percentages and numbers of thymic Foxp3+ Treg 14, 15, thereby establishing that DC are dispensable for the generation of nTreg. Moreover, CD11c-DTA mice retained functional peripheral Treg 15. However, closer examination of the blood circulation and LN of cDC-deficient animals and comparison to their littermate controls revealed

a twofold reduction in the frequencies of Treg out of total CD4+ T cells, whose numbers are unaltered 15 (Fig. 1A). This reduction of peripheral Foxp3+ Treg was also observed upon conditional cDC ablation, as achieved through repetitive diphtheria toxin (DTx) treatment of [CD11c-DTR>WT] BM chimeras (Fig. 1B) 16, thereby confirming recent reports that established the critical role of cDC Nintedanib (BIBF 1120) in promoting the homeostatic Treg proliferation 13, 17. Re-examination of Treg frequencies in cDC-deficient animals by staining for both Foxp3 and CD25 revealed a twofold reduction of Foxp3+CD25+ (double positive) Treg in all organs tested, including the spleen (Fig. 1C–E). Interestingly though, the decrease of splenic Foxp3+CD25+ Treg was uniquely associated with a concomitant elevation in the frequencies of Foxp3+CD25− (single positive) cells out of CD4+ T cells (Fig. 1E). This finding explains the reason why the splenic Foxp3+ T-cell compartment of cDC-deficient CD11c:DTA mice had, in the previous studies, appeared unaffected 14, 15. Collectively, these data establish that although cDC are not required for the generation of nTreg in the thymus, they are – in agreement with recent reports 13, 17 – critically involved in the maintenance of peripheral Foxp3+CD25+ Treg.

[47] Also CotH colocalize with GRP78 during R. oryzae invasion of endothelial cells. More importantly, a mutant of R. oryzae with attenuated expression of CotH exhibited reduced ability to invade and damage endothelial cells and had reduced virulence in a DKA mouse model of mucormycosis. Of special interest is the wide presence of CotH among Mucorales and its absence from other known pathogens.[47] Collectively, ZVADFMK the unique interaction between GRP78/CotH and the enhanced expression of GRP78 by glucose and iron concentrations often seen in hyperglycaemic, DKA and other acidosis patients likely explain the increased susceptibility of these patient populations to mucormycosis. As mentioned above,

patients with elevated available serum iron, be it free iron or ferrioxamine iron, are at high risk of acquiring mucormycosis. Experimental data strongly indicated that the use of iron chelators GSK-3 inhibitor review that are not utilised as xeno- siderophores by Mucorales can be of benefit in treating the disease alone or as an adjunctive therapy.[29-31, 48] In 2005, deferasirox became the first orally bioavailable iron chelator approved for use in the US

by the FDA to treat iron overload in transfusion-dependent anaemia. This lead to the off label use of deferasirox in treating advanced cases of mucormycosis with reported success as an adjunctive therapy mainly in diabetic patients with ketoacidosis.[49] However, a subsequent phase II, double-blind, randomised, placebo-controlled trial of adjunctive deferasirox therapy that enrolled a total of twenty patients failed to demonstrate a

benefit of the combination regimen in patients with mucormycosis.[50] In fact significantly higher mortality rates were found in patients randomised to receive deferasirox at 30 (45% vs. 11%) and 90 days (82% vs. 22%, P = 0.01). It is imperative to note that although this study represents the first completed clinical trial of evaluating a novel treatment option for mucormycosis, it suffered from major imbalances between the two study arms with patients receiving deferasirox were more likely than placebo patients to have active malignancy, neutropenia, corticosteroid therapy and less likely to have received additional antifungal, making the results of this pilot GNAT2 trial hard to interpret.[51] Thus, conclusions regarding the use of deferasirox cannot be drawn from this small study. Indeed subsequent studies to the Phase II clinical trial continue to suggest the successful use of deferasirox as an adjunctive therapy against mucormycosis especially in DKA patients.[52, 53] Therefore, only a large, Phase III trial, potentially enrolling only diabetic or corticosteroid-treated patients (as suggested by the animal studies[30] and anecdotal studies [49, 52]), and excluding cancer/neutropenia patients, could further elucidate the safety and efficacy of initial, adjunctive deferasirox (and other iron chelators) for the treatment of mucormycosis.

The authors have no financial conflicts of interest. “
“We previously reported that Staphylococcus aureus avoids killing within macrophages by exploiting the action of Toll-like receptor 2 (TLR2), which leads to the c-Jun N-terminal kinase (JNK)-mediated

inhibition of superoxide production. To search for bacterial components responsible for this selleck chemical event, a series of S. aureus mutants, in which the synthesis of the cell wall was interrupted, were screened for the level of JNK activation in macrophages. In addition to a mutant lacking the lipoproteins that have been suggested to act as a TLR2 ligand, two mutant strains were found to activate the phosphorylation of JNK to a lesser extent than the parental strain, and this defect was recovered by acquisition of the corresponding wild-type genes. Macrophages that had phagocytosed the mutant strains produced more superoxide than those engulfing the parental strain, and the mutant bacteria were more efficiently killed in macrophages than the parent. The genes mutated, dltA and tagO, encoded proteins involved in the synthesis of d-alanylated wall teichoic acid. Unlike a cell wall Cabozantinib mw fraction rich in lipoproteins,

d-alanine-bound wall teichoic acid purified from the parent strain by itself did not activate JNK phosphorylation in macrophages. These results suggest that the d-alanylated wall teichoic acid of S. aureus modulates the cell wall milieu for lipoproteins so that they effectively serve as a ligand for TLR2. Invading microbial pathogens compete with host organisms in the regulation of innate immunity.1–5 They try to circumvent host immune responses to achieve effective infection and prolonged survival through, for example, inhibition of signalling pathways for the activation of nuclear factor (NF)-κB and mitogen-activated

protein kinases, which induce the transcription of genes coding for antimicrobial substances and pro-inflammatory cytokines.1–3 Some bacteria evade phagocytosis by immune cells or do not submit once phagocytosed: they inhibit phagosomal click here maturation or escape from phagosomes to avoid digestion by lysosomal enzymes.6 To overcome such microbial actions against immune responses, host immune cells adopt alternative strategies, such as the induction of autophagy, in which cytoplasmic bacteria are resealed with membranes and subjected to lysis.7–9 It is important to clarify the mechanisms underlying the conflict between microbial pathogens and host organisms to develop novel and effective medicines against infectious diseases. We previously reported that Staphylococcus aureus inhibits the production of superoxide in macrophages to evade killing after phagocytosis, through Toll-like receptor 2 (TLR2)-mediated phosphorylation of c-Jun N-terminal kinase (JNK).

74,75,77In vitro studies of superficial and invasive selleck products clinical Malassezia isolates consistently demonstrate susceptibility to amphotericin B and antifungal triazoles, whereas flucytosine and echinocandins appear to be inactive.11,65,71,90–92 Thus, in the absence of experimental and comparative clinical data and the large clinical experience with invasive Candida infections, fluconazole or voriconazole may be rational

first-line options for antifungal chemotherapy with an amphotericin B product as back-up for refractory or life-threatening infections (Table 1). While the duration of treatment has not been defined, we would advocate a course of 14 days of effective antifungal MK-1775 concentration therapy after the last positive blood culture and catheter removal as recommended for invasive Candida infections and optional switch from initial intravenous to oral therapy depending on the individual patient’s clinical response.79 Very little is known about the detailed morbidity

and mortality of invasive Malassezia infections. While Malassezia can cause severe disease and fatal cases have been reported in untreated patients, available series of catheter-associated fungaemia in premature neonates and in immunocompromised non-neonatal patients suggest low attributable mortality with appropriate management.12,21,56,80,93,94 Oxalosuccinic acid “
“The amino acid derivative 2-hydroxyisocaproic

acid (HICA) is a nutritional additive used to increase muscle mass. Low levels can be detected in human plasma as a result of leucine metabolism. It has broad antibacterial activity but its efficacy against pathogenic fungi is not known. The aim was to test the efficacy of HICA against Candida and Aspergillus species. Efficacy of HICA against 19 clinical and reference isolates representing five Candida and three Aspergillus species with variable azole antifungal sensitivity profiles was tested using a microdilution method. The concentrations were 18, 36 and 72 mg ml−1. Growth was determined spectrophotometrically for Candida isolates and by visual inspection for Aspergillus isolates, viability was tested by culture and impact on morphology by microscopy. HICA of 72 mg ml−1 was fungicidal against all Candida and Aspergillus fumigatus and Aspergillus terreus isolates. Lower concentrations were fungistatic. Aspergillus flavus was not inhibited by HICA. HICA inhibited hyphal formation in susceptible Candida albicans and A. fumigatus isolates and affected cell wall integrity. In conclusion, HICA has broad antifungal activity against Candida and Aspergillus at concentrations relevant for topical therapy.

Irradiated splenocytes that were used as a source of APCs in our experiments could

be treated with Ficoll–Hypaque and separated from the CD4+ T cells only after 1 day in cultures. In preparation for later experiments, Fig. 1(c) was included, showing that anergy could be demonstrated using beads instead of antigen to stimulate secondary cultures. In addition to proliferative unresponsiveness, Th1 cells stimulated with antigen in the presence of n-butyrate demonstrated a 37–77% decrease in IL-2 and a 26–55% decrease in interferon-γ secretion when stimulated in secondary culture with three different stimulation indices (Fig. 1d). Hence, n-butyrate-induced anergy PI3K inhibitor was demonstrated by a loss of both antigen-induced proliferation and cytokine production. It has

been reported previously that n-butyrate increased p21Cip1expression in antigen-stimulated Th1 cells.8 However, p21Cip1 is also induced in antigen-stimulated Th1 cells in the absence of n-butyrate. Consequently, the kinetics of p21Cip1 up-regulation was studied in antigen-stimulated Th1 cells in the presence and absence of n-butyrate during the 6-day primary cultures to compare the two groups for learn more any possible difference in p21Cip1 expression. When antigen was added in the initiation of the primary culture (day 0), p21Cip1 was up-regulated in control Th1 cells by day 1, remained high on day 2, but decreased significantly by day 3 and was back to resting levels by day 5 (Fig. 2a). In contrast, when antigen was added on day 0 and n-butyrate was added on day 1, the p21Cip1 levels remained

elevated in anergic Th1 cells during the entire 6-day primary culture. p27Kip1 is another cdk inhibitor thought to play a role in T-cell anergy. As expected, p27Kip1 was high in resting Th1 cells. Its level decreased with the antigen stimulation and was later restored to resting levels in control Th1 cells by day 5 of the primary cultures. In contrast, p27Kip1 levels failed to be completely restored in Th1 cells incubated with antigen and n-butyrate in 6-day primary cultures (Fig. 2b). Hence, because p21Cip1 rather than p27Kip1 was high in the anergic Th1 cells at the end of the 6-day primary cultures, subsequent experiments however were focused on the role of p21Cip1 in maintaining proliferative unresponsiveness. The kinetics of other cell cycle proteins was also studied to assess their possible involvement in n-butyrate-induced T-cell anergy. No significant differences between the antigen-stimulated control and anergic Th1 cells were observed in the expression of cdk2, cdk4, cdk6, cyclin D2, cyclin D3 and cyclin E (Fig. 2b). In summary, the kinetics studies on cell cycle proteins revealed that the most detectable difference between anergic and control Th1 cells was the high level of p21Cip1 maintained throughout the primary cultures in the anergic Th1 cells. Localization of proteins such as p21Cip1 in the cell can have important functional consequences.

Nevertheless, the heterologous aromatic side chains at the P2 anchor motif resulted in the reduction of the binding affinity of variant peptides to H-2Kd molecules (Fig. 1c and Supplementary material,

Fig. S3). The structural similarity of side chains is required for anchor motifs to dock peptide epitopes into the pocket of MHC class I molecules. The peptide–MHC binding interface is more tolerant of the subtle change of the functional group at the anchor motif of natural amino acids, such as phenylalanine (F) replacing tyrosine (Y). The binding capacity of peptides to MHC class I molecules had become the most important consideration for the epitope prediction of immunoinformatical programmes. selleck chemical Most servers developed for the prediction of epitopes were based on peptide–MHC binding affinity.27–30,32 As in much of the documented research

into peptide–MHC class I binding experiments, we have mapped CD8 T-lymphocyte variant Selleckchem KPT 330 epitopes without obvious anchor motifs of primary amino acid sequences, which were still recognised by virus-specific CD8 T lymphocytes (Fig. 1c and 2). Anchor motifs and peptide–MHC binding affinity are not sufficient to predict all the protective epitopes from viral antigens22,45,46 (Fig. 2). T-cell receptor binding of expressed specific peptide–MHC class I complexes on the surfaces of infected cells is less understood in the field of T-lymphocyte recognition.26,31,55 We have found that the efficient binding of peptides to MHC class I molecules does not always ensure the recognition of peptide–MHC class I complexes by either virus-specific or peptide-specific CD8 T lymphocytes (Figs. 1, 2 and 3). Peptide–MHC class I binding and TCR recognition are actually two distinct antigen presentation events given that variant peptides with amino acid substitutions at the TCR contact site obscure the recognition of specific CD8 T lymphocytes without DNA ligase compromising their binding capacity to MHC class I molecules even in the presence of analogous side chains of natural amino acids (Figs 1c, 2a and 3b). Parallel to two distinct antigen presentation

events: peptide-MHC class I binding and TCR recognition, physiochemical distributions of amino acids from MHC class I-restricted epitopes represent two separated interfaces of discrete physiochemical characteristics. Conserved and hydrophobic amino acids are identified at P2 and P9 anchor motifs on the peptide-H-2Kd interface (Supplementary material, Fig. S4a), whereas the peptide–TCR interface expresses variable amino acid distributions in terms of hydropathy and isoelectric indexes (Supplementary material, Fig. S4). Extensive data from X-ray diffraction crystal structures of different alleles of MHC–peptide–TCR complexes provides detailed binding and recognition information of interfaces among peptide, MHC and TCR.

The differences in the complexity of the CD8+ T-cell response or the influence

of background genes (e.g. extent of IFN-γ production) may account for the results. Using LCMV infection of naïve C57BL-6-PKO mice Lykens et al. recently showed that heightened antigenic stimulation is responsible for exaggerated T-cell activation [[49]]. They suggested that perforin-dependent cytotoxicity, in addition to promoting viral clearance, regulates T-cell activation by modulating Ag presentation [[49]]. Despite the differences in susceptibility of naïve BALB/c and C57BL/6 PKO mice to LCMV infection, we also observed massive CD8+ T-cell expansion and accelerated LCMV-induced mortality in GP33-vaccinated compared with naïve C57BL/6-PKO PI3K inhibitor mice (data not shown). Thus, the vaccine-induced sensitization to mortality associated with PKO memory CD8+ T cells after LCMV infection is not restricted to BALB/c background. In addition, functional exhaustion of antigen-specific CD8+ T cells is not always associated with chronic infection [[50, 51]]. Chronic infection may be pathogen or host specific and it does not necessarily lead to Ag-specific CD8+ T-cell

exhaustion in all the cases. Although we observed lesser degree of “exhaustion” as characterized by TNF and PD-1 expression in GP283-specific CD8+ T cells compared with NP118-specific CD8+ T cells, viral control was not achieved in the absence of perforin in both cases (Fig. 5). In the absence of perforin, the phenotype of GP283-specific CD8+ T cells appeared “less exhausted” at the time we analyzed them could reflect the selleck compound extent that these cells can regulate cytokine production. In addition, it remained to be elucidated whether encounter with antigen is similar between the NP118- and GP283-specific memory CD8+ T

cells in the PKO mice, not just initially, but throughout the infection course. Previous studies using different models of infection showed that protective immunity mediated by pathogen-specific CD8+ T cells did not correlate with immunodominance hierarchies after infection [[36, 37]]. Based on the results with PKO mice vaccinated with dominant NP118 epitope, we expected that massive antigen-specific memory CD8+ T-cell expansion contributed to the LCMV-induced mortality independent of epitope specificity. Interestingly, Protirelin PKO mice vaccinated with subdominant GP283 epitope survived the LCMV infection even though they contained similar starting memory CD8+ T-cell numbers and underwent similar expansion in numbers as NP118-specfic CD8+ T cells. These results suggested that epitope specificity dictates the LCMV-induced mortality in vaccinated PKO mice. Furthermore, we also observed less cytokine dysregulation, in particular IFN-γ, by GP283-specific CD8+ T cells following LCMV infection. It is unclear which specific parameter(s) influence the cytokine profile of these GP283-specific CD8+ T cells and subsequent vaccine-induced mortality in PKO mice.

Multiparity induces transferable-specific hypo-responsiveness or even true tolerance to either HY or paternal alloantigens.53,54

Placental products, be them placental PCI-32765 manufacturer extracts or water-soluble material obtained from these, co-injected with alloantigenic cells, induce systemic antigen-specific LyT2+ Ts.81 These were traced in the first pregnancy in mice and in rats by Baines and Liburd. Similarly, antigen-specific MHC-restricted Ts were found in humans.82 Controversies about in vitro assays can still be traced in proceedings of the Gusberg meeting.83 In the 1980s, we studied, in detail, the in vitro properties and mode of action of these suppressor cells (specificity, mediation by a soluble factor). A part of these studies was carried out with anti I–J antisera, as many other labs working on suppression did at the time. Lee Hood’s demonstration that the I–J region does not exist while properties of the suppressor buy Fostamatinib factor(s) of

Gershon and Cantor were more and more improbable doomed Ts. For an excellent revision of the history of Ts, see references.84,85 We nevertheless still tested/published the role of Ts in CBA × DBA/2 matings.51 As reviewed, in,86 the CD25 and Foxp3 markers again boosted Ts on the forefront. Yet the I–J trauma lead to a more benign denomination of ‘regulatory T cells’ (Tregs), rather than ‘CD4+ Ts’, which we first saw in 1981, but termed ‘inducers’ .87 CD8+ cells are still important partners, as shown in studies by Arck, Clark and coworkers.88 Aluvihare and Darasse convincingly demonstrated that CD4+ CD25+ elimination causes foetal deaths in allopregnancy by transfer or direct in vivo experiments.89,90 Saito traced/ quantified Foxp3 cells Sinomenine (T regs) in human decidua as well as regulatory NK/T cells.91 Robertson and coworkers92 showed that the Foxp3

marker decreases in unexplained infertility endometrial biopsies. These, and Fainbolm, detected periodic T reg modulation during the menstrual cycle, peaking in the late follicular phase.93,94 For Fainbolm, T regs from patients with RSA are ‘functionally deficient’,93 and T reg decidual recruitment correlates with expression levels of CCL3, CCL4, CCL5, CCL22, and CX3CL1.90 Finally, placenta-dependent CD8+ T regs have been demonstrated by Shao et al.,95 and this is reminiscent of earlier data in mice about LyT2 Ts.81 Could the placenta escape immune attack by resisting effector cell lysis? We have discussed the Fas/Fas ligand interaction. Membrane and soluble HLA-G (sHLA-G) also play a role, including sHLA-G secretion by the MHC-syncytiotrophoblast. Moreover, trophoblasts (and choriocarcinomas) are resistant intrinsically to cell-mediated lysis.96–98 This resistance is independent of HLA-G.99,100 The once debated soluble factors96,101,102 had properties which fits with what is now known of soluble HLA-G, be it sHLAG1/ G2 characteristics.

LDH activity was analyzed using the commercially available Cytotoxicity Detection Kit (Roche). For three-dimensional skin models, 1×106 human oral keratinocytes (TR146) were seeded on inert filter substrates (Nunc, polycarbonate filter, 0.4 μm pore size, 0.5 cm2) in antibiotic/antimycotic-free defined keratinocyte growth medium (Lonza) for 9 days. After 5 days inert filter substrates were lifted to the air–liquid interface and basal cells were fed through the filter substratum. Epithelium was treated with IFN-γ (300 U/mL), IL-17, IL-22, TNF-α (50 ng/mL each), IL-22/TNF-α combination or Th22 supernatant directly before infection

with 2×106 Candida yeasts for 12 h. Light microscopical studies Luminespib in vitro were performed as previously described using paraffin-embedded oral epithelium specimens 34, 35. Statistical analysis was done using One-way ANOVA and Bonferroni’s Multiple Comparison Test as post test. Statistically significant differences were defined as *p≤0.05, **p<0.01,

***p<0.001. This work was supported by the German Research Foundation STI571 cost (DFG) EY97/2-1 and SFB Tr22. We thank Kerstin Holtz and Gaby Pleyl-Wisgickl for outstanding technical assistance. Conflict of interest: The authors declare no financial or commercial conflict of interest. “
“Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine–polycytidylic acid (poly I:C) and polyadenylic–polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN-β autocrine

loop, dsRNA-elicited Carbohydrate IFN-β production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN-β at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN-β produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN-γ production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3−/− mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1−/− mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN-β production and contribute to the antitumoral response.