Additional features were detected in this tumor that are known to be associated with an unfavorable find more prognosis, including loss of

p16 expression and gains of chromosomes 1q and 12. The patient experienced the most rapid downhill course reported to date for intracranial Ewing sarcoma, developing multiple extracranial metastases at 2 months and dying 6 months after the initial operation. “
“V. Leinonen, A. M. Koivisto, S. Savolainen, J. Rummukainen, A. Sutela, R. Vanninen, J. E. Jääskeläinen, H. Soininen and I. Alafuzoff (2012) Neuropathology and Applied Neurobiology38, 72–86 Post-mortem findings in 10 patients with presumed normal-pressure hydrocephalus and review of the literature Aims: Neuropathological features of idiopathic normal-pressure hydrocephalus (iNPH) are poorly characterized. Brain biopsy during life may help in the differential diagnosis of dementia, but post-mortem validation of biopsy findings is scarce. Here we review and

report brain biopsy and post-mortem neuropathological findings in patients with presumed NPH. Methods: We evaluated 10 patients initially investigated by intraventricular pressure monitoring and a frontal cortical biopsy for histological and immunohistochemical assessment GS 1101 as a diagnostic procedure for presumed NPH. Results: Out of the 10 patients, eight were shunted and seven benefited. Until death, six had developed severe and two mild cognitive impairment. One was cognitively unimpaired, and one was mentally retarded. Three subjects displayed amyloid-β (Aβ) aggregates in their frontal cortical biopsy obtained at the initial procedure. One of these patients developed Alzheimer’s disease during a follow-up time of nearly 10 years. One patient with cognitive impairment and NPH suffered from corticobasal degeneration. In six patients

Arachidonate 15-lipoxygenase various vascular lesions were seen at the final neuropathological investigation. Five of them were cognitively impaired, and in four vascular lesions were seen sufficient in extent to be considered as causative regarding their symptoms. Conclusions: The frequent finding of vascular pathology in NPH is intriguing, suggesting that vascular alterations might be causative of cognitive impairment in a notable number of patients with NPH and dementia. Brain biopsy can be used to detect Aβ aggregates, but neuropathological characteristics of iNPH as a distinct disease still need to be discovered. “
“Wnt activation in medulloblastomas is associated with good outcome. Upfront testing and risk-adapted stratification of patients will be done in future clinical studies. In a cohort of 186 pediatric medulloblastomas our aim was to identify the optimal methods in standard clinical practice to detect this subgroup. Nuclear accumulation of ß-catenin was analyzed by immunohistochemistry (IHC). DNA of FFPE tissue was amplified by PCR for single-strand conformation polymorphism analysis and direct sequencing of CTNNB1 exon 3.

Cancers expressing hCG/subunits have poor prognosis and adverse survival. Thus, immunological approaches against hCG have applications for control of fertility and for treatment of terminal cancers. Various mechanisms by which hCG exercises its action are discussed. These include

its role as autocrine growth promoter, inhibitor of apoptosis, promotor of angiogenesis, invasiveness, and protection against rejection by the immune system. The article reviews various vaccines developed for control of fertility and for therapy of advanced-stage cancers expressing ectopically hCG/subunits. Also reviewed are the recombinant fully humanized and chimeric antibodies usable CP-690550 for emergency contraception, as vacation contraceptive, and as therapeutic antibodies for treatment of cancers. Human chorionic gonadotropin (hCG) is a unique hormone. Its existence was discovered by Selmar Aschheim and Bernhard Zondek in 1927.1 They reported that the blood and urine of pregnant women contained a gonad-stimulating substance. On injecting this substance subcutaneously in immature female mice, it led to follicular

maturation, luteinization, and haemorrhage into the ovarian stroma. This procedure became known as the Ascheim Zondek pregnancy test, the very BGB324 cell line first of its kind. hCG is made by a woman soon after conception. Robert Edwards, who got the Nobel Prize in Medicine (for year 2010), and his colleagues were the first to report the presence of hCG in the culture fluid of early embryos from eggs fertilized in-vitro.2 It plays a critical role in implantation

of the embryo onto the uterus. MYO10 Marmoset embryos exposed to antibodies against beta subunit of hCG do not implant, whereas the same embryos exposed to normal globulins implant normally.3 A similar role of hCG in implantation of the embryo in humans is provided by the observation that sexually active women of reproductive age immunized with a vaccine generating antibodies against hCG do not become pregnant and their menstrual cycles remain regular without lengthening of the luteal phase.4 For a long time, hCG was believed to be made and secreted in normal healthy women only in pregnancy. Recent observations by Alexander group5 indicate the expression of hCG by human endometrial cells during luteal phase. It is not unlikely that hCG made during this phase of the cycle prepares the endometrium to receive the fertilized egg. An unexpected site of expression of hCG and its subunits (α and β) in men and in non-pregnant women is in a variety of cancers such as lung cancer,6 bladder carcinoma,7 colorectal carcinoma,8 pancreatic carcinoma,9 breast cancer,10 cervical carcinoma,11 oral cancers,12 vulva/vaginal cancers,13 prostate cancer,14 and gastric carcinomas.15 Patients harboring such cancers have poor prognosis and adverse survival.

This observation underlines the need to be cautious to extrapolate in vitro studies with Tregs to in vivo situations. Besides the issue of level of FOXP3 expression, duration of expression may be an important facet determining the function of

induced Tregs. The reduced effectiveness of the induced FOXP3 T cells may be time-dependent as earlier in vitro studies report that continuous levels of FOXP3 are required to convert naive T cells into Tregs with full effectiveness 6. In this setting of systemic inflammation, 24 h seems to be too short to procure the full molecular and transcriptional changes necessary for suppression. On the other hand, it does seem to be sufficient to inhibit the cell from dividing after TCR stimulation in vitro. Accordingly, FOXP3 may act as an intrinsic regulator during inflammation, preventing collateral damage by temporarily silencing activated T Bioactive Compound Library cells. In conclusion, during systemic inflammation due to cardiac surgery in children, FOXP3+ T cells lose suppressive capacity. While these cells are anergic to TCR stimulation, the transiently increased expressed FOXP3 is not capable of taking on a suppressive function. Furthermore, the inflammatory milieu in which Tregs exert their action after cardiac surgery inhibits

their suppressive activity. This study illustrates the functionality of FOXP3+ T cells in a human model of inflammation and underlines the requirement of more human in vivo systems to understand the properties and potential of induced FOXP3+ Tregs in human disease. Children admitted to our hospital Ponatinib for surgical repair of either a VSD or an ASD were enrolled in this study. Patients were excluded from the study if at the time of admission they had received steroids within 2 wk before surgery, had signs of infection or had a documented immunodeficiency. Informed consent was obtained from the parents of children Morin Hydrate participating in the study. The medical ethics committee approved this study (METC 03/049-K, UMC Utrecht, The Netherlands). General anesthesia was always implemented using a standard technique

involving high-dose sufentanil, midazolam, pancuronium, dopamine and milrinone. All patients were given a single dose of dexamethason (1 mg/kg) after induction of anesthesia. Non-pulsatile CPB was used, the standard pump flow rate was 2.8 L/m2/min. Combined alpha and pH stat management of acid–base status was used during CPB. The cardioplegia procedure was standardized using St. Thomas’ solution. After weaning from CPB, all patients remained intubated and ventilated and were admitted to the pediatric intensive care for further management. All patients were treated by the same surgical team. Blood samples were obtained from a central venous catheter at the following time points: immediately after insertion during anesthetic induction (T1), at the end of the CPB (T2) and at 4 h (T3), 24 h (T4) and 48 h after surgery (T5).

S. G. M. received honoraria for lecturing and travel expenses for attending meetings and has received financial research support from Bayer, Biogen

Idec, Sanofi-Aventis, Bayer Schering, Merck Serono, Novo Nordisk, Genzyme, MSD and Teva. All authors declare no relevant conflicts of interest. “
“Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important component of the inflammasome, Selleckchem MLN0128 functioning as an adaptor protein that facilitates the recruitment and activation of procaspases that in turn promote the maturation of interleukin-1β (IL-1β) and IL-18. Despite initial focus on the inflammatory properties of ASC there is emerging evidence that highlights the IWR1 importance of ASC in facilitating adaptive immune

responses. However, the cellular and molecular basis for the involvement of ASC in adaptive immunity remains largely unexplored. We have previously demonstrated that activated ASC-deficient T cells have dampened proliferative responses. We have therefore explored the underlying cellular mechanism(s) by which ASC regulates T-cell proliferation. We show that under activating conditions (anti-CD3/CD28 stimulation) in bulk T-cell cultures the presence of ASC−/− CD4+ T cells is sufficient to suppress the proliferative responses of neighbouring T cells. Furthermore, ASC−/− CD4+ T cells upon activation exhibit a suppressive cytokine profile, with elevated production of IL-10 and reduced secretion of T helper type 1 cytokines, interferon-γ and IL-2. This increase in IL-10 secretion within the activated ASC−/− CD4+ T-cell compartment Vasopressin Receptor was not associated with a proportional increase in conventional Foxp3+ regulatory T (Treg) cells. Interestingly, when equal numbers of fluorescence-activated cell sorted ASC+/+ and ASC−/− Treg cells (CD4+ CD44intermediate/high CD25+) were activated in vitro, the ASC−/− fraction produced significantly more IL-10 than their wild-type counterparts, suggesting that ASC−/− Treg cells have greater suppressive capacity. Collectively,

these results imply that the ASC may influence the development and functioning of Treg cells. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an integral component of the inflammasome, a cytosolic multiprotein platform that facilitates the activation of pro-inflammatory caspases, which in turn promote the maturation and subsequent secretion of interleukin-1β (IL-1β) and IL-18.1,2 ASC is a simple adaptor protein with two linked protein–protein interaction domains of the death domain superfamily: an N-terminal pyrin/PAAD death domain and a C-terminal caspase recruitment domain, which interact with the different NOD-like receptors, the sensory elements of the inflammasome and pro-caspase-1, respectively.3–5 These two domains enable ASC to function as an essential link between the sensor protein and effector molecules during inflammasome assembly.

In the latter case, LSCI data should be expressed as raw perfusion units, but not as a function of baseline.

Overall, correction for BZ makes data analysis more complicated Ganetespib mw without improving reproducibility. Among the different techniques reviewed, each has advantages and drawbacks. Microscopy-derived techniques are semi-quantitative, implemented in small devices that can be used at the bedside; they are mostly used to assess morphology rather than the function of the microvasculature. On the other hand, the advantage of laser Doppler and laser speckle techniques is that they can be coupled with various reactivity tests to challenge microvessels. However, these tests do not specifically assess distinct pathways, but provide an overall assessment of microvascular function. Indeed, recent studies have shown that the mechanisms underlying common reactivity tests (i.e., Ach iontophoresis, PORH, and LTH) are complex and involve several different pathways [15]. Besides a deeper exploration into their mechanisms, these tests should be standardized if they are to be used as surrogate markers of microvascular function. Another approach which has not been explored in this review concerns signal processing. Indeed, cutaneous blood flow has been studied through several processing tools, such as the Fourier transform and the wavelet transform [25]. Other methods, such as multifractality and sample entropy, have

recently been applied to LDF signals [67]. Dasatinib purchase In conclusion, different Casein kinase 1 techniques have been developed in the past 30 years to assess microvascular function. Although optical microscopy-derived techniques (such as nailfold videocapillaroscopy) have found clinical applications, they mainly provide morphological information

about the microvessels. Laser Doppler techniques coupled to reactivity tests are widespread in the field of microvascular function research. PORH and LTH have been shown to be reliable tests, although their underlying mechanisms are not fully understood yet. Despite its wide use as a specific test of endothelial function, acetylcholine iontophoresis has many limitations. In a general way, all these tests suffer from a lack of standardization and show highly variable reproducibility according to the skin site, recording conditions and the way of expressing data. Recent techniques like laser speckle contrast imaging are promising tools, although further work is needed to determine the strength of the technique. We thank Dr. Alison Foote for editing the manuscript. None declared. Matthieu Roustit is assistant professor of Clinical Pharmacology at Joseph Fourier University and Pharmacologist at the Clinical Research Center of the Grenoble University Hospital, France. His main areas of interest include methodological issues regarding the study of skin microvascular function, especially with laser Doppler and laser Speckle contrast imaging.

Immunized ER-β−/− and WT donors

LNC were sorted for CD11b/CD11c+ DC and CD11b/CD11c− (non-DC) fractions. The DC fractions were from ER-β−/− or WT mice, whereas non-DC fractions were all from WT mice. Cells from various ER-β−/− and WT donors were mixed with the ratios of DC (3%) and non-DC (97%) based on the immune cell composition Epacadostat of non-manipulated immunized donor LNC, then stimulated with autoantigen before adoptive transfer into ER-β ligand- or vehicle-treated recipient mice (Fig. 5A). As shown in Fig. 5B, ER-β ligand-treated mice adoptively transferred with WT DC (green) had reduced EAE disease severity compared with ER-β ligand-treated mice that were adoptively transferred ER-β−/− DC (orange). These results demonstrated that ER-β ligand treatment during the effector phase of EAE acts at least in part on ER-β-expressing DC. Previously, our lab showed that ER-β ligand treatment was neuroprotective in active EAE without altering cytokine production of autoantigen-specific selleck chemical immune cells in the periphery and without reducing the level of CNS inflammation. Specifically, ER-β ligand treatment preserved axon densities and myelin staining late in disease despite persistent inflammation in the CNS 16. However, it remained unknown whether qualitative differences might exist in the inflammatory

infiltrates of ER-β ligand-treated EAE mice. Therefore, in the present study, we examined immune cells in the CNS of EAE mice treated with ER-β ligand. We found that ER-β ligand treatment conferred clinical protection in the effector phase of adoptive EAE and reduced the percentage of DC in the target organ. DC isolated from the CNS of ER-β ligand-treated EAE mice exhibited decreased TNF-α production. Finally, we showed that ER-β ligand treatment in EAE conferred disease protection through ER-β expressed

on DC. This is the first study elucidating an in vivo immunomodulatory role for ER-β during autoimmune demyelinating disease. DC are emerging as critical mediators of inflammation in a variety of organ-specific autoimmune diseases such as rheumatoid arthritis, psoriasis, and EAE due to their efficient antigen-presenting ability 20, 26, 28–31. CNS DC are critical to EAE Thiamine-diphosphate kinase pathogenesis, as DC infiltrates in the CNS during EAE preferentially localize with effector TC at sites of inflammation and they alone can activate infiltrating naïve TC to differentiate and perpetuate inflammation 20, 28. Our finding of quantitative and qualitative effects of ER-β ligand treatment on CNS DC, which occurred in a setting of improved clinical and neuropathologic disease corroborates other studies showing that CNS DC play a critical role in EAE disease severity 32–34. Further, ER-β ligand treatment can now be considered as a novel treatment strategy targeting DC in the CNS. DC are excellent targets for organ-specific autoimmune diseases for several reasons.

1 g greater LVMI (95% CI 0.5–1.6).118 However, analysis of the NHANES III data did not show any association between high dietary phosphate intake and mortality in 1105 CKD patients (HR 0.98 per 100 mg/dL increase (95% CI 0.93–1.03)).119

Few clinical trials have looked at lowering dietary phosphate absorption in participants with normal phosphate levels to prevent the complications of CKD-MBD. An experimental study using a rat model of CKD-MBD reported animals with reduced GFR fed a grain-based diet, MG-132 solubility dmso compared with standard synthetic casein animal diets, had lower serum phosphate, urinary phosphate excretion and serum levels of FGF-23.120 The same investigators conducted a cross-over trial in nine patients (mean eGFR 32 mL/min) and compared vegetarian and meat diets. They reported decreased urine phosphate excretion, lower serum phosphate and decreased FGF-23 levels with a vegetarian diet

after 1 week.121 This study also highlighted that higher dietary phosphate intake was associated with increased FGF-23. Dietary phosphate counselling for CKD patients can be complex and patients are often confused by the multitude of recommendations. Simplifying the approach by asking them to eat more grains and less meat and less pre-prepared or packaged foods may potentially lead to increased dietary adherence and subsequent improved phosphate homeostasis. One study educating ESKD patients on dialysis to avoid phosphate-containing food additives resulted in modest improvements in hyperphosphataemia.122 However, further dietary studies are required in CKD patients as additives are increasingly being added Stem Cells inhibitor to processed and fast foods and the effect of dietary modifications on serum phosphate levels in early CKD is unclear. Despite the rapidly growing body of literature suggesting phosphate dysregulation is associated with increased morbidity and mortality in CKD, what remains to be established is whether early intervention

to prevent phosphate retention can impact on the development of the adverse clinical outcomes associated with CKD-MBD. To date, there has not been an adequately powered, placebo-controlled, multicentre RCT evaluating Fenbendazole the effects of phosphate-lowering therapy on reduction of CVD burden in CKD patients. One of the first questions to help design an RCT addressing phosphate homeostasis in early CKD would be to determine the trigger for intervention or the abnormality that one should aim to correct. Hyperphosphataemia occurs late in CKD, at which point arterial or ventricular function may be impaired, so the approach should probably be to intervene before this occurs. Rising phosphate levels within the normal range maybe both a trigger for intervention and its target, but phosphate levels undergo circadian and dietary variation and fasting levels may also be uninformative, so this approach may not prove valuable.

TLR4-deficient BMDM stimulated with MRP8 also showed lower M1/M2, suggesting that the effect of MRP8 upon M1 dominancy might be partly through TLR4. Migration assay and phalloidin selleck kinase inhibitor staining of MΦ revealed that deletion of MRP8 resulted in less migration and stress fiber formation. Conclusion: Myeloid-lineage cell-derived MRP8 potentially contributes to glomerular injury through intraglomerular cell-cell crosstalk affecting MΦ characterization.

WEI QING-XUE WEI1, GAO LEI-PING1, WAN YI-GANG2 1Changshu Hospital of Traditional Chinese Medicine; 2Nanjing Drum Tower Hospital Introduction: Interstitial fibrosis (IF) is a vital factor leading to renal failure, which is aggravated by the imbalance between extracellular matrix (ECM) components production and degradation. Matrix metalloproteinases AZD6244 research buy (MMPs) play a key role in ECM degradation while TGF-beta1 is a crucial regulator of ECM

protein synthesis and degradation. Although it has been confirmed that Uremic Clearance Granules (UCG), a natunal phytomedicine, are clinically effective in improving renal failure in China, the mechanisms remain a challenge. This study aims to investigate the effects and mechanisms of UCG on IF by regulating MMPs synthesis and TGF-beta1 signaling in vivo. Methods: The rats with IF, induced by adenine and unilateral ureteral obstruction (UUO) on day 15, were randomly divided into 4 groups: the sham-operated group, the vehicle group, the UCG group, and the enalapril group. All rats were killed on day 35 after administration. The rats’ proteinuria, urinary N-acetyl-D-glucosaminidase (UNAG), blood biochemical parameters and RF morphological changes were examined. The protein expressions of ECM component such as collagen type IV (col-IV),

MMPs synthesis such as MMP-2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1, as well as TGF-beta1 signaling molecules including TGF-beta1, TGF-beta RI, TGF-beta RII, Smad2/3, phosphorylated-Smad2/3 (p-Smad2/3), Smad4, Smad6 and Smad7, were observed respectively. Results: Adenine Thiamet G administration and UUO induced severe renal damage, as indicated by renal dysfunction, proteinuria and the marked histopathological injury in the tubules and interstitium. This was associated with MMP-2/TIMP-1 imbalance and TGF-beta1/Smad signaling activity, as shown by up-regulation of the protein expressions of TGF-beta1, TGF-beta RI, TGF-beta RII, Smad2/3, p-Smad2/3 and Smad4, as well as down-regulation of the protein expression of Smad7. UCG treatment, however, significantly attenuated renal dysfunction and tubulointerstitial fibrosis. It regulated the protein expressions of MMP-2/TIMP-1, and suppressed the protein expressions of TGF-beta1, TGF-beta RI, p-Smad2/3 and Smad4, whereas it enhanced the protein expression of Smad7. Furthermore, the effects of UCG are stronger than those of enalapril partly.

49–2.76,

P = 0.02). Up to the last follow-up, 61 patients (83.5%) had returned to their previous work. The Rosén–Lundborg model can be a useful and simple tool for the evaluation of the functional outcome after nerve injury and repair temporally reflecting the processes of regeneration and reinnervation. © 2010 Wiley-Liss, Inc. Microsurgery, 2011. “
“In this report, we present our experience with subcutaneous rt-PA injection for salvage of free radial forearm flaps with vascular compromise. Three patients underwent reconstruction of defects of the soft palate or the lateral tongue with a free radial forearm flap. Patients underwent on average two attempted operative revisions with thrombectomy and intravenous heparin injections. After recurrent venous thrombosis Fulvestrant molecular weight 3–6 days after surgery, rt-PA (Alteplase

2 mg; 1,160,000 IE) was injected subcutaneously at multiple sites into the compromised flap as final attempt. In all three patients, successful thrombolysis with no or only partial soft tissue loss was achieved after subcutaneous injection of rt-PA. We therefore suggest subcutaneous rt-PA injection as an additional tool in managing difficult and recurrent cases of venous thrombosis in free flap head and neck reconstruction. © 2013 Wiley Periodicals, Inc. Microsurgery 33:478–481, 2013. “
“It is thought that the small intestine may provide a scaffold for pancreas regeneration. Herein, we investigated whether fetal pancreatic tissue could be BEZ235 ic50 transplanted into the segmental intestine in rats. Anidulafungin (LY303366) Fetal pancreases from firefly luciferase transgenic

Lewis rat embryos (embryonic day 14.5 and 15.5) were transplanted into streptozotocin (STZ)-induced diabetic wild-type Lewis rats. As a scaffold for pancreatic development, rat small intestinal segments were utilized after the removal of mucosa, and fetal pancreases were grafted into the luminal surface through the stoma. We also transplanted fetal pancreases into the omentum. The survival of transplanted fetal pancreases was monitored by luciferase-derived photons and blood glucose levels. Transplanted fetal pancreas-derived photons were stable for 28 days, suggesting that transplanted fetal pancreatic tissues survived and that their intestinal blood supply was maintained. © 2010 Wiley-Liss, Inc. Microsurgery, 2010. “
“Department of Plastic Surgery, Loma Linda University Medical Center, Loma Linda, CA. Gabriel A. Del Corral is currently at Division of Plastic Surgery, University of Pennsylvania Health System, Philadelphia, PA Early free flap coverage in lower extremity trauma is a practice largely supported by research that may be outdated and is frequently impractical due to logistics, resuscitation efforts, and associated injuries. Our objective was to re-evaluate this paradigm to determine whether reconstructive timing impacts outcome in modern clinical practice.

cerevisiae was independent from TLR7, TLR9, or the IRF1-transcription factor, while largely requiring BMS-907351 chemical structure dectin-1 (Fig. 4). Yeast lysates in complex with the cationic lipid carrier DOTAP recapitulated, in a dose-dependent way, the MyD88-dependent induction of IL-12p70 noted with live S. cerevisiae. Pretreatment of these fungal lysates with RNAse almost completely abrogated induction of IL-12p70, whereas DNAse treatment was comparatively less effective and proteinase K treatment was totally ineffective

(Supporting Information Fig. 3). Moreover, combined treatment with RNase and DNase almost completely suppressed the IL-12p70-inducing ability of extracts. Interestingly, IL-23 and TNF-α, induction was partially MyD88-dependent, in agreement with the observation that various

Afatinib ic50 TLR agonists can collaborate with dectin-1 agonists in the induction of optimal IL-23 [33] or TNF-α levels [34]. Similar signaling requirements were found when using heat-killed C. albicans in place of live S. cerevisiae as a stimulus (Supporting Information Fig. 4), although the latter stimulus was considerably more potent than killed C. albicans at inducing cytokines. Collectively, this data suggested that IL-12p70 production in response to whole yeast requires a TRL7- and TLR9-initiated pathway involving MyD88 and IRF1. Although stimulation with yeast nucleic acids did result in TLR7/9-dependent TNF-α and IL-23 secretion, these TLRs did not apparently make a significant contribution to the overall ability of whole fungi to induce these cytokines. Since TLR7 and TLR9 are endosomal receptors, we investigated whether IL-12p70 responses were induced by yeast in the absence of functional UNC93B1, a chaperone protein that

mediates the translocation of intracellular TLRs (including TLR3/7/8/9) to the endosomal compartment. To this end, we used BMDCs from 3d mice that have a point mutation in a transmembrane domain of UNC93B1, which renders the protein incapable of interacting with intracellular TLRs [35-37]. TLR7/9 double knock-out mice were also used in these experiments. Adenosine Notably, IL-12p70 responses were totally abrogated in the absence of functional UNC93B1 or in cells lacking both TLR7 and TLR9, while neither IL-23 nor TNF-α responses were affected (Fig. 5). Similarly, cytochalasin D, an agent that disrupts actin microfilaments and prevents phagocytosis, totally abrogated the release of IL-12p70, but not IL-23 or TNF-α, by BMDCs after stimulation with S. cerevisiae (Fig. 6). In addition, similar effects were observed after BMDCs treatment with bafilomycin A, a drug that prevents phagosomal acidification. Thus phagocytosis, phagosomal acidification, and TLR7/9 translocation to the endosomal compartment were all required for the production of IL-12p70, but not IL-23 or TNF-α in response to fungal recognition. To determine whether signaling through the TLR7 pathway has a role in host defense against C. albicans, we used an i.v.