The appreciation that tissue-derived CD103+ DCs in mice, and BDCA3hi DCs in humans, appear to be functionally

and developmentally very closely related to CD8+ DCs, but do not express CD8, has recently lead to the proposal to define this lineage of DCs by their expression of XCR1 [5, 6], a chemokine receptor that is conserved between the different DC subsets and across the species. In www.selleckchem.com/products/forskolin.html addition to this proposed DC lineage, DCs expressing high levels of surface CD11b appear to be functionally biased toward promoting MHC class II-restricted CD4+ T-cell responses [7]. However, only a proportion of splenic CD11bhi DCs express CD4, and tissue-resident CD11bhi DCs are characterized by CD205 expression rather than CD4 [8]. Consequently, the cohort of CD11bhi DCs appears considerably more heterogeneous compared with the relatively well-defined CD8+/XCR1+ lineage [4, 9]. This view is supported by the diverse range of transcription factors and molecules that have been implicated in the development of CD11bhi DCs [10]. Interestingly, it

was recently shown that differential this website requirement for Notch 2 receptor signaling defines two distinct lineages within the CD11bhi DC population [11]. The Notch 2 receptor signaling-dependent CD11bhi DC population is characterized by high-level expression of ESAM, an immunoglobulin superfamily molecule previously associated with neutrophil extravasation [12], and ESAMhi CD11bhi DC have been described as potent inducers of CD4+

T-cell priming [11]. Conversely, ESAMlo CD11bhi DCs develop independently 5-FU chemical structure of Notch 2 receptor signaling and have a gene expression signature resembling that of monocytes [11]. However, exactly how ESAMhi and ESAMlo CD11bhi DCs diverge during development and what factors control Notch 2 receptor signaling in CD11bhi DCs remains obscure. In this issue of the European Journal of Immunology, Beijer et al. [13] have described an unexpected role for vitamin A in promoting the development of these newly described ESAMhi CD11bhi DCs within the spleen. Vitamin A, or retinol, is acquired through dietary intake and stored predominantly within the liver before release into the circulation. Upon conversion of circulating vitamin A into its active metabolite retinoic acid (RA) by retinaldehyde dehydrogenase (Raldh), RA acts as a transcriptional regulator, binding retinoic acid receptors (RAR), and retinoic X receptors (RXR) that are located in the nucleus. The binding of RA to RAR/RXR heterodimers facilitates the recruitment of coactivators and the formation of transcriptional complexes that dock onto RA response elements within the regulatory regions of target genes, which in turn initiates transcription [14]. Vitamin A has long been appreciated for its essential role in host immunity, and more recently has gained considerable attention as a major player in controlling intestinal immunity [15].

,

Hercules, CA, USA). The primer pairs utilized for qPCR are shown in Table 1. The data are presented as the mean + SD and are representative of at least two independent experiments that employed at least four mice in each group, unless otherwise indicated. Data were analyzed using the Student’s t-test. A value of P < 0·05 was considered significant. The administration of ES proteins to the airways induced immune cell infiltration, particularly neutrophil and lymphocyte infiltration, into the lung (Figure 1a,b). The level of IL-17 cytokines in bronchial alveolar lavage (BAL) was increased profoundly after six repetitions of ES protein airway treatment, as compared with what was noted in the OVA-only treatment group (Figure 1c). In addition, the cells from the ES protein-treated Gefitinib research buy mouse lung could generate more IL-17 cytokines than those of the OVA-only treatment group (Figure 1d). The cells of the lung draining lymph node could secrete more IL-17 cytokine than those of the mesenteric lymph node cell in response to OVA re-stimulation. This finding demonstrated that the ES protein contained some molecule that could activate Th17 cells. However, we were unable to detect any difference in the spleen cells between the ES proteins and the mice treated only with OVA. In

addition, the levels of Th2 cytokines (IL-4, -5 and Buparlisib -13) were not increased after ES protein treatment (data not shown). To determine the mechanism underlying immune cell recruitment by ES proteins, we measured IL-6, CXCL1, MDC (CCL22), TARC (CCL17) and GM-CSF gene expression levels from lung epithelial cells using ELISA, real-time PCR and RT-PCR. It is well known that CXCL1 and IL-8 (CXCL8) perform a key role in the recruitment of neutrophils during lung inflammation (25). In addition, IL-17 levels are very closely related to IL-6 levels (25,26). The lung epithelial cell line (MLE12) cells could generate IL-6 and CXCL1 as a response to ES protein treatment; we also observed the same result in a study of

primary lung epithelial cells (Figure 2a). The ES proteins induced lung inflammation via the production of IL-6 and CXCL1. 5-FU In addition, The GM-CSF, TARC and MDC gene expressions in the MLE12 cells were increased by parasite ES proteins (Figure 2b). These chemokines are also related to neutrophil and T-cell and B-cell recruitment. To determine whether or not the ES protein can activate TLR, we analyzed TRIF KO and MyD88/TIRAP KO mouse embryonic fibroblast (MEF) cells after ES treatment. The ES proteins were shown to enhance the expression of IL-6 and CXCL1 in wild-type (WT) MEF, similar to what was observed in lung epithelial cells. However, we did not find that the ES protein could not enhance IL-6 and CXCL1 levels in TRIF KO MEF cells (Figure 3a,b, Supplementary Figure S1). We assessed this again with ES proteins after the administration of RNase A and C treatment to MEF cells. The results we observed, however, did not differ between the RNase-treated and nontreated samples.

This study aimed to validate and extend these findings in an independent sample. Methods: Eighty-six completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow-up was obtained. Utilizing a dual-colour interphase fluorescence in situ hybridization assay, 1q gain was assessed using Bacterial Artificial Chromosome probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone

complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment DNA Damage inhibitor of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas. “
“G. F. Simões and A. L. R. Oliveira (2010)

Neuropathology and Applied Neurobiology36, 55–70 Alpha motoneurone input changes in dystrophic MDX mice after sciatic nerve transection Background: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy. At present, a lot is known about the muscular degeneration in DMD, but few studies have focused on the effects on the central nervous system. In this sense, retrograde changes in the microenvironment GPCR Compound Library supplier around motor neurones in the spinal cord may contribute to the pathogenesis of the dystrophinopathies. Aims: The aim of this study was to investigate synaptic alterations and glial reactivity in the microenvironment close to spinal motor neurones in a DMD animal model. Methods: Six-week-old male MDX mice were subjected to left sciatic Nutlin3 nerve transection.

The axotomy was performed after the muscular degeneration/regeneration cycles previously described in such animal models. C57BL/10 mice were used as the control. Seven days after surgery, the animals were sacrificed and the lumbar spinal cords processed for immunohistochemistry using antibodies to the major histocompatibility complex of class I (MHC I), synaptophysin, IBA-1 and glial fibrillary acidic protein (GFAP). Results: MHC I expression increased in both strains after axotomy. Nevertheless, the MDX mice displayed significantly lower MHC I up-regulation. With respect to GFAP expression, the MDX mice showed greater astrogliosis as compared with C57BL/10 mice. The MDX mice displayed a significant decrease in synaptophysin expression. Indeed, the ultrastructural quantitative analysis showed more intense synaptic detachment in MDX mice, indicating a reduction in synaptic activity before and after axotomy. Conclusions: The reduction in active inputs and increased gliosis in MDX mice may be associated with the muscle degeneration/regeneration cycles that occur postnatally, and could contribute to the seriousness of the disease.

oryzae compared to CAS or ABLC monotherapy.[26] Furthermore, based on preclinical studies, Reed et al. showed that patients with rhino-orbital-cerebral mucormycosis treated with CAS and ABLC therapy had superior success and survival time compared with patients who received ABLC monotherapy.[73] The same group of investigators[74] showed that the enhanced efficacy of LAmB with micafungin (MFG) or anidulafungin combination therapy

in treating DKA mice with disseminated mucormycosis is a class effect. Triple therapy for mucormycosis consisting of LAmB, MFG and the iron chelator deferasirox was superior to monotherapy or dual therapy treatments. Triple therapy improved survival of mice by 40% compared to 0–11% for AZD4547 price all other

treatments.[75] Given the resistant phenotype of Mucorales with conventional drugs, the potential for triple therapy in mucormycosis should be further investigated in preclinical and clinical studies. Although PSC shows good in vitro susceptibilities against Zygomycetes, the in vivo efficacy of PSC in immunosuppressed murine models of disseminated mucormycosis is substantially variable as well as species- and dose-dependent.[44-48] DZNeP in vitro In order to evaluate its role in combination therapy, Rodriguez et al.[76] investigated the efficacy of PSC in combination with AmB. Findings showed that low doses of AmB (0.3 mg/kg, once daily) combined with PSC (40 mg/kg, once daily) prolonged survival, but it was not superior to the high-dose of administered AmB (0.8 mg/kg, once daily), allowing reduction of the AmB dose and similar efficacy levels with AmB monotherapy. A most recent in vivo combination study, using a non-lethal murine model of cutaneous mucormycosis caused by R. oryzae, showed that TAC

combined with PSC reduced significantly cutaneous lesions and fungal burden compared to the animals administered VRC alone.[77] To date, there is no adequate clinical evidence on the use of VRC as a single agent or in combination therapy. For this reason, additional studies are required to explore further the role of VRC to improve the prognosis and outcome of the patients who develop invasive mucormycosis. Beta-glucan is an essential cell wall component of fungi that lies beneath a Galeterone dense layer of mannan coat. The inner beta-glucan layer is targeted by the dectin-1 receptor of immune cells, mediating the innate immune response, and by the echinocandin class of antifungal drugs. Lamaris et al. [78] showed that the beta-glucan unmasking effect of CAS enhanced the activity of PMN against A. fumigatus and R. oryzae as well as other non-Aspergillus hyphae. The effect of PMN against A. corymbifera, R. microsporus and R. oryzae under the influence of LAmB and ABLC was also investigated in another in vitro study. While LAMB exhibited synergistic activity with PMN in inducing hyphal damage only to R.

The late pre-B click here (fraction D) and immature B (fraction E) compartments had an approximately 40 and 50% decrease in numbers when compared to wild-type controls (p < 0.001 and p = 0.002, respectively). This pattern

of reduction in cell numbers matched that what we had previously observed at comparable stages of B-cell development on a BALB/c background [19]. However, unlike BALB/c IgHa.ΔD-iD mice where the absolute numbers of mature fraction F B cells in the bone marrow is halved when compared with those of wild-type; in C57BL/6 IgHa.ΔD-iD mice, the absolute numbers of fraction F B cells was fully normalized when compared with those from wild-type C57BL/6 control mice (p = 0.67) (Table 1). In order to distinguish between normalization of mature B-cell numbers due to the enhanced prevalence of B cells bearing IgM with charged, arginine-enriched CDR-H3s versus selection and increased survival for mature B cells that bear IgM with a more neutral CDR-H3 repertoire that could result from DH inversion or increased www.selleckchem.com/products/idasanutlin-rg-7388.html N addition (potential somatic

selection for “normality”); we evaluated 52 in-frame VDJCμ transcripts isolated from C57BL/6 ΔD-iD bone marrow fraction F B cells (Supporting Information Table 2). This permitted direct comparisons between the CDR-H3 loops of fraction F B cells using the same IgHa.ΔD-iD allele, but differing by C57BL/6 versus BALB/c genetic background. The pattern of reading frame usage, the prevalence of sequences lacking identifiable DH sequence, and the prevalence

of N addition was statistically indistinguishable between the IgHa.ΔD-iD repertoires expressed by the two mouse strains. Additionally, both the global prevalence of arginine, tyrosine, and valine in CDR-H3 and the relative distribution of CDR-H3 sequences containing one or more of these representative amino acids were statistically indistinguishable (Fig. 9A and B). The prevalence of neutral CDR-H3 loop sequences did not increase. To the contrary, the prevalence of highly charged and highly hydrophobic CDR-H3 loops in fraction F on the C57BL/6 background proved higher than on the BALB/c background (12.5% versus 9.2% and 3.8% versus 0; respectively) (Fig. 9C and D). We conclude that the normalization of IgHa.ΔD-iD fraction F B-cell numbers in C57BL/6 mice reflected an increase in the numbers SPTLC1 of mature, recirculating cells bearing both highly charged, arginine-enriched CDR-H3 loops and highly hydrophobic CDR-H3 loops (derived from alternative reading frames) when compared with those in BALB/c mice. Although the potential diversity of the CDR-H3 component of the immunoglobulin H-chain repertoire is astronomical, previous evaluation of the developing repertoire in BALB/c mice has allowed us and others to identify several key elements where there is strong evidence of either developmental or ontological constraints on this diversity (reviewed in [20]).

They could additionally damage myocardial tissue, because MHC class I proteins

disappeared in the central infarction sites, whereas their expression was conserved, but weaker in the surrounding peri-necrotic zones of the MI 1 week after an acute coronary event when compared to myocardial tissue sections of persons who died 5 weeks after an acute coronary event. It LBH589 cost suggests susceptibility of peri-infarction zones for NK cell killing mediated by cytotoxic mediators. GNLY+ CD3+ cells and rarely GNLY+ CD56+ cells reach the apoptotic APAF-1+ cardiomyocytes in the border infiltration zone of persons who died 1 week after the acute coronary event and could participate in the apoptosis of these cells. Accordingly, apoptotic single-stranded DNA–positive cells were found in the border zones and granulation tissue cells in the infarct region by Akasaka et al. [7]. But, it is unlikely that GNLY+ cells cause significant cardiomyocytes apoptosis because of their small

numbers. In addition, later after the MI, the APAF-1+ apoptotic myocardial cells are found without close contact with GNLY+ cells, suggesting implementation of GNLY-independent mechanism of cellular loss. A formation of apoptosome after the binding of APAF-1 protein with cytochrome C could induce caspase 9 dimerization and autocatalysis [32]. Indeed, apoptotic markers (caspase 3 and apoptotic bodies) are present in the surviving zone of the heart, remote from the infarct region, as early as day 1 after MI and persist for up to 1 month

[3, 33]. Additionally, Mephenoxalone Akt inhibitor on day 7 after an acute coronary event, the significant increase in the percentage of peripheral blood GNLY+ NK cells enables GNLY-mediated K-562 apoptosis, as the mechanism attributed to perforin-mediated cytotoxicity [31]. GNLY probably accesses the K562 target cell cytoplasm through perforin pores or by other mechanisms that involve sublytic perforin concentrations in agreement with Lettau et al. [18], because an additive effect between GNLY- and perforin-mediated cytotoxicity has not been found. This suggests that they probably use the same mechanism for entering cells. On day 14, in patients with NSTEMI, GNLY expression, as well as perforin expression [31], in all peripheral blood lymphocyte subpopulations was the lowest and it was reflected in negligible NK cell apoptotic activity against K-562 cells. The lower percentage of GNLY-positive NK cells in patients with NSTEMI on day 21 as compared to day 7, correlated well with mostly perforin-mediated NK cell killing as a redundant apoptotic mechanism [27]. At the end of a 1-month rehabilitation period in patients with NSTEMI, we again found significant participation of GNLY in K562 apoptosis as a result of restored GNLY expression in peripheral blood NK cells.

[6] Significant efforts are now focused on determining the mechanism(s) that mediate the progressive changes in phenotype and

function of antigen-specific T cells as they develop in response to both acute and chronic pathogens. Here we review our current understanding of transcriptional regulatory mechanisms of genes directly related to effector and memory functions and highlight potential mechanisms for the generation of phenotypically distinct memory T-cell subsets. It is believed that memory T cell heterogeneity has evolved as a mechanism for partitioning memory-associated functions into specialized cells to protect against a range of pathogens and routes of exposure. Memory CD8 T cells Selleckchem Sunitinib Palbociclib chemical structure that populate non-lymphoid tissues and provide immediate recall of effector functions are loosely categorized as effector-memory (Tem) cells. Tem cells maintain down-regulation of the molecules CD62L and CCR7 and serve as the first line of defence against pathogen re-exposure. In contrast, memory CD8 T cells that express CD62L and CCR7 and preferentially home to lymphoid tissues are referred to as central-memory cells (Tcm). The preferential lymphoid homing of Tcm cells is believed to facilitate their encounter with antigen-presenting dendritic cells, thereby generating a self-renewing source of cells with effector functions, which can then migrate to the site of infection.[14-17] Importantly,

many of the differentially acquired traits of Tem versus Tcm cells, including CD62L- and CCR7-mediated lymphoid homing, are the result of differential transcriptional regulation of gene products from the ‘on-off-on’ subset of genes (Fig. 1b). A current challenge for the field is to determine how acquired transcriptional programmes, those common among all memory cells as well as the transcriptional programmes that are unique to memory subsets, are maintained during cell MRIP division of memory T cells. Drawing upon insights from other developmental systems, epigenetic modifications may provide a transcriptional regulatory mechanism that can be propagated

during homeostatic cell division of memory cells.[18, 19] Recently several laboratories have demonstrated that epigenetic modifications, namely histone modifications and DNA methylation, modulate transcriptional activation of effector molecules via the restriction of access to chromatin by transcription factors and polymerase. Our current understanding of epigenetic regulation of memory cell function has come from studies that have focused on the mechanisms controlling expression of effector molecules such as the genes for interferon-γ (IFNg), interleukin 2 (IL-2) granzyme b and perforin.[20-25] As these genes become transcriptionally up-regulated, the proximal promoter region loses repressive epigenetic marks (DNA and histone modifications).

One µg of the mRNA was reverse-transcribed into cDNA with a master mix of oligo-dT (20 µg/ml, Roche, Meylan, France), deoxyribonucleotide (dNTP) (16 µmol/ml;

Invitrogen), RNase block (20 U/ml; Stratagene, Amsterdam, selleck chemicals the Netherlands) and reverse transcriptase (50 U/ml; Invitrogen). The cDNA was then PCR-amplified with β-actin housekeeping gene-specific primers (R&D Systems) designed to amplify a portion of the coding sequences (7·5 pmol/µl), dNTP (8 µmol/ml) and Taq polymerase (1·25 U/ml; Sigma-Aldrich). Raji B cells were used as positive amplification controls and a master mix without added cDNA was used as a negative control. The cDNA expression was detected on a 1·5% agarose gel. The final product of the β-actin housekeeping gene was 298 base pairs (bp) in size. To analyse AID gene expression, a nested reverse transcription–polymerase chain reaction (RT–PCR) assay was used. We selected the conserved active site of cytidine check details deaminase as the primary target. Primers

were designed as follows: external 5′ GAAGAGGCGTGACAGTGCT 3′ (sense) and 5′ CGAAATGCGTCTCGT AAGT 3′ (anti-sense); internal 5′ CCTTTTCACTGGACTTTGG 3′ (sense) and 5′ TGATGGCTATTTGCACCCC 3′ (anti-sense). The final product of the AID gene was 656 bp in size [27]. Quantification of band intensity was carried out by Image J version 1·42q software (National Institutes of Health, Bethesda, MD, USA) and expressed as the mean of the optical density of five independent blots ± standard error

of the mean (s.e.m.). Band intensity was normalized to the optical density of the actin-β housekeeping control loaded onto the same blot. Interexperimental comparisons of the cell culture conditions were analysed by a Mann–Whitney unpaired test. Differences were considered statistically significant for P < 0·05. The peripheral blood of normal healthy donors (n = 15) showed large variation in the frequencies of the peripheral B cell subsets (Fig. 1c), with 68·3 ± 8·9% IgD+CD27-, 11·5 ± 5·2% IgD+CD27+ and 22·9 ± 7·8% IgD-CD27+ B cells. The IgD-CD27+ B cells population could be subdivided further into 13·1 ± 3·2% IgD-CD27+IgG+ or IgD-CD27+IgA+ and 9·8 ± 3·6% IgD-CD27+IgM+ B cells. The optimal concentration of activators in this culture Resveratrol system required a balance between the best readout (IgA synthesis determined by ELISA) and B cell pathway activation (determined by Western blot). In agreement with previously published culture conditions, we selected the concentrations of 50 ng/ml for sCD40L, 100 ng/ml for IL-10 and 0·2 ng/ml for TGF-β. Although sCD40L or IL-10 alone increased IgA production significantly by approximately 10-fold and approximately 30-fold, respectively, IgA production after the simultaneous addition of sCD40L and IL-10 was statistically similar to that observed with addition of IL-10 alone (Fig. 2a). An additive effect was observed for IgA production when sCD40L was used at 50 ng/ml and IL-10 from 80 to 120 ng/ml (Fig. 2b).

“
“We highlight a case of chronic skenitis leading to the formation of Urethral diverticulum. A young nulliparous woman presented with dysuria, intermittent hematuria and a 3 cm cystic swelling adjacent to the left distal urethra. Aspiration of the cyst was done initially. Excisional biopsy was followed when it recurred. Ku-0059436 clinical trial Urethral diverticulum was revealed when the excisional operation traced up to left distal urethral wall. The cystic swelling urethral diverticulum was completely enucleated. The pathology report showed fibrous tissue with cystic spaces lined by squamous epithelium with inflammation, which was consistent with a urethral diverticulum.

The presenting symptoms and signs of female urethral diverticulum are often diverse and easily overlooked,

we have to keep in mind that cases with unusual age, location and presentation can also exist. “
“Objectives: The aim of the present study was to determine whether administration of zolpidem, a nonbenzodiazepine sedative-hypnotic agent, at night would improve the nocturia unresponsive to alpha-blocker monotherapy in Navitoclax price men with lower urinary tract symptoms (LUTS). Methods: This was a prospective observational study comprised of 39 men aged 50 years and older. The study inclusion criteria were age more than 50 years, and nocturia twice or more per night after taking alpha-blockers for more than 8 weeks. A total of 39 patients met the criteria and constituted the study cohort. Pittsburgh Sleep Quality Index (PSQI), International Prostate Symptom Score (IPSS), frequency Alectinib mouse volume chart (FVCs) and uroflowmetry were recorded. Patients were given 10 mg alfuzosin and 10 mg zolpidem once at night for the 8 weeks. Results: There were no serious side-effects in any patient. Nocturia decreased from a baseline (3.1 ± 0.1) to 8 weeks (1.6 ± 0.2) (P = 0.001). After treatment, global PSQI scores and severe sleep disorders improved. Storage and voiding symptoms including total IPSS scores and quality of life index improved. Nocturnal urine volume and functional bladder capacity improved. Maximum flow rate, voided

volume increased and residual urine volume decreased. Conclusion: Combined zolpidem and alpha-blocker therapy resulted in a subjective and objective reduction in nocturia episodes when given to men with nocturia unresponsive to alpha-blocker monotherapy. “
“Objectives: A Federal Drug Administration-approved, compassionate-use, investigational new drug single-subject trial was conducted to evaluate the safety and clinical outcomes of intravesical instillation of liposomes in a woman with ulcerative interstitial cystitis/painful bladder syndrome (IC/PBS). Methods: After obtaining informed consent, the 48-year-old woman, diagnosed with ulcerative IC/PBS, received four weekly instillations of intravesical liposomes. Subsequently she was evaluated for 8 weeks post bladder instillation. Results: No side effects or adverse events were reported during the 12 week study period.

This showed that moDCs induced greater numbers of IFN-γ selleck kinase inhibitor producing T cells and fewer IL-4-producing cells than cDCs. Co-culture of T cells with both DC subsets selectively induced greater IFN-γ responses than either component DCs subset, but this was not seen

for IL-4 (Fig. 5D). This suggests moDCs are more efficient than cDCs at driving CD4+ T cells to produce IFN-γ but can collaborate with cDCs to augment this. Lastly, in this and other studies 24, moDCs have been identified as major producers of TNF-α. To assess whether this cytokine influenced the priming of IFN-γ-producing cells, we cultured cDCs or moDCs with SM1 T cells in the presence or absence of a TNF-α-neutralizing antibody (Fig. 5E). These experiments show that neutralizing TNF-α reduces the numbers of IFN-γ-producing cells induced by moDCs but not by cDCs. Surprisingly, neutralizing TNF-α only moderated Th1 development when moDCs were cultured alone with SM1 T cells. This diminution was not seen when moDCs were co-cultured with cDCs (Fig. 5E). Therefore, moDCs can present antigen to CD4+ T cells and promote their differentiation to become IFN-γ-producing T cells. Th1 responses are characterized by the induction of IFN-γ and are essential for clearing intracellular

infections such as those caused by STm. Our studies indicate that moDCs accumulate in the T zone after STm infection, have encountered live bacteria, can present antigen to T cells and in their Wnt inhibitor absence Th1 responses are impaired. Finally, our data suggest that moDCs can act in conjunction with cDCs to perform this function. It is significant that the accumulation of moDCs is dependent upon bacterial viability rather than virulence. This offers some explanation as to why hk STm vaccines induce Th2 features but poor Th1 responses 32. The importance of viability has also been demonstrated for the recruitment of TipDCs in response to L. monocytogenes17. This suggests that inducing moDCs is likely to be a key requisite aminophylline of Th1-promoting adjuvants and that characterizing moDC induction

is likely to provide a measure of their success. Interestingly, other subunit components of the bacterium that act through TLRs, such as FliC, do not induce moDC accumulation to the same degree and this parallels the lack of Th1 response seen to flagellin in vivo 6, 33, 34. We have also observed differential Th1 or Th2 T-cell priming to OVA when presented within the bacterium or as an alum-precipitated protein respectively 35. This highlights that T-cell fate is not necessarily an intrinsic property of the T cell but dependent upon the signals received from DCs during priming. Bacterial virulence is not an important requirement for driving moDC accumulation since virulent bacteria and bacteria attenuated through two distinct mechanisms, aroA-deletion resulting in histidine auxotrophy and ssaV-deletion resulting in impaired secretion of Salmonella Pathogenicity Island II effectors, all induced moDCs to similar levels 24 h after infection.