Clustered protocols use two or three injections at each weekly visit, thus see more reducing the total time required to reach

maintenance dose (usually in 7–8 weeks). Rush desensitization protocols have been also described, but are used less often for aeroallergens than for hymenoptera venoms (see below) in view of the higher rate of systemic reactions, including anaphylaxis [16]. Dose reductions are made for delayed or missed injections, during a symptomatic period (for example during the pollen season) or following large local reactions (≥ 10 cm) and systemic reactions. General health, adverse events, changes in medication and peak expiratory flow are monitored prior to administration of SCIT. An observation period of 1 h after the injection is mandatory, with peak expiratory flow testing prior Pexidartinib concentration to discharge. However, severe ‘non-immediate’ reactions can occur up to 24 h after allergen injection. SLIT.  SLIT involves placing the vaccine in solution (drop preparation) or tablet

form under the tongue for 1–2 min followed by swallowing. Patient selection for sublingual immunotherapy (SLIT) is identical to that for SCIT. The safety profile of SLIT is superior to SCIT, and serious side effects such as anaphylaxis have been extremely rare [17–23]. Many patients develop minor discomfort in the early phase of treatment, including oropharyngeal pruritis and angioedema, which may require treatment with an antihistamine, but these symptoms usually settle with continued administration of the vaccine. The indications, contraindications and general considerations in administration of

SLIT are the same as described under SCIT. However, there are some special considerations listed as follows. One particular preparation (Grazax; ALK Abello, Denmark) currently licensed in the United Kingdom contains fish gelatin. It may be used cautiously in patients with a history of fish allergy, but is absolutely contraindicated in patients with history of anaphylaxis to fish. Dosage and regimens.  Sublingual immunotherapy has been used for Inositol monophosphatase 1 several aeroallergens including pollens, house dust mite and cat. The optimum dosage, duration and frequency of administration have not yet been established. Sublingual immunotherapy involves a much higher dose of allergen than SCIT. The cumulative monthly dosage of SLIT used in clinical studies has been variable, but has been 0·6–500 times greater than customary SCIT [18]. Several dosing regimens have been employed, including daily (fixed or incremental dosing) [24–26], three times per week [27] and weekly [28]. With seasonal allergens such as pollen, treatment has been given preseasonally, co-seasonally, pre- and co-seasonally and perennially. Prolonged preseasonal administration induces greater clinical benefit, and if treatment is continued perennially, clinical and immunological responses improve in subsequent years of treatment [29,30].

The CT and TT genotypes were pooled to avoid classes with very small numbers, because only two individuals had the TT genotype (one in the case group and one in the control group). This type of pooling was also used in other studies. Therefore, distinguishing between the dominant or co-dominant model of inheritance for the C and T alleles at this locus and their effect on the studied variables is difficult. However, as expected,

the effect of ethnicity was not observed in the HLA-DR3 /DR4 allele frequency, because these alleles usually confer high susceptibility to T1AD in all populations [4, 5]. The association of C1858T polymorphism with T1AD and other autoimmune diseases was proposed to depend upon the pathogenic LYP-W620 variant that shows increased phosphatase activity and is a gain-of-function inhibitor of T cell signalling buy CX-5461 [9]. In our study, this polymorphism was associated with an increased frequency of GAD65 autoantibody and TG autoantibody when the entire cohort (T1AD patients + healthy controls) was considered. Although the T1AD patients had higher frequencies of pancreatic and non-pancreatic autoantibodies than the healthy controls, there

was no association between the *T1858 allele and other islet and organ-specific autoantibodies. Thus, although the frequency of organ-specific autoantibodies in our population RAD001 order was similar to what has been reported previously for Caucasians, this frequency did not depend on the presence of the T1858 allele, except for the autoantibodies against the pancreas and thyroid. The C1858T PTPN22 polymorphism was associated with T1AD susceptibility SPTLC1 and autoimmune thyroid disease. Autoantibodies specific to other organs and tissues were frequent in T1AD carriers, predominantly the thyroid glands. The 1858T PTPN22 polymorphism was associated with a higher frequency of GAD65 and TG autoantobody. Allelic variants

in the 5′-proximal region of the IL-21 gene were not related to T1AD susceptibility and other autoimmune diseases. The HLA-DR3 and/or DR4 alleles predominated in T1D patients. We thank Dr George S. Eisenbarth of the Barbara Davis Center for review of the manuscript. We thank Greci S. Paula, Adriana Rosa, Maria de Fátima Sanches and Maria José Pegoraro of the Laboratório de Investigação Médica LIM 18 and to LIM-25, LIM-42, LIM-56 and Hospital das Clínicas da Faculdade de Medicina da USP for technical assistance. This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP, process 2006/06390-1. All authors declare they have no conflicting interests. “
“The human homologue of the mouse double minute 2 (MDM2) is known to be overexpressed in a variety of human malignancies. As one of E3 ubiquitin–protein ligases, MDM2 interacts with the tumour suppressor p53 by mediating ubiquitination and degradation of p53.

[11] with

some modifications. In brief, CD27 signals were visualized first with brown chromogen using Bond Polymer Refine Detection kit (Leica Biosystems), and then, using the same tissue slides, T cells were stained using anti-CD3e antibody with purple chromogen using Bajoran Purple Chromogen System (Biocare Medical, Concord, CA, USA). Thus, only CD27-positive B and plasma cells were left to be revealed in brown colour. Total B and plasma cells were detected in serial sections using conventional immunostain for CD79a (JCB117; Leica Biosystems) [12]. After examining ten high-power fields in each case, the percentage of the memory and plasma cells Tanespimycin mouse to total B and plasma cells was estimated. DNA extraction, IgH gene amplification click here and subcloning.  Genomic DNA was extracted from formalin-fixed, paraffin-embedded sections by overnight digestion with proteinase K. DNA of all cases was found to be of satisfactory quality as confirmed by PCR for the beta-globin gene. A seminested strategy was used for PCR amplification of the VH genes using a consensus primer for conserved framework-2 (FR2A) and a consensus primer for the J region (LJH and VLJH). These primers have been used most commonly for VH gene analysis of formalin-fixed, paraffin-embedded

tissue specimens tissue [13–15]. The PCR products were stained with ethidium bromide and run on agarose gels. To minimize any amplification bias, genomic DNA from

each case was amplified in multiple PCR runs (n > 80), and the amplified products were mixed in one tube and then subcloned for DNA sequencing. Subcloning of the PCR products was performed with pGEM T-easy vector (Promega, Madison, WI) using DNA that was excised from a polyclonal band in the agarose gel and purified. Recombinant clones were randomly picked-up and amplified by PCR using primers encompassing the insert. Those showing the expected insert size were then sequenced using an ABI Prism Big Dye Terminator kit (Applied Biosystems, Foster City, CA) on an automatic DNA sequencer. More than 50 polyclonal clones from each case of SS, MD and chronic sialolithiasis were sequenced. Sequence analysis.  The DNA sequences were aligned with IgH sequences from IgBLAST (available at http://www.ncbi.nlm.nih.gov/igblast/). ADAM7 Clones that showed non-productive rearrangements were excluded from the present analysis. VH gene sequences deviating more than 2% from that of the corresponding germline gene were defined as mutated [16]. Statistical analysis.  Statistical evaluation of data from the two groups was performed using Fischer’s exact test (two-tailed). Analysis was performed using the statistical package JMP (SAS Institute Inc., Cary, NC, USA). Clinical features of SS (n = 3), IgG4-related sclerosing sialadenitis (n = 3) and sialolithiasis cases (n = 3) are shown in Table 1.

We applied gain- and loss-of-function strategies to delineate the functional roles of miR-106b in MB. Luciferase reporter assay was conducted to confirm target gene of miR-106b. Expression of miR-106b was overexpressed in MB, and was significantly associated with its host gene MCM7 (p=0.020). Transfection

of miR-106b inhibitor in MB cell lines markedly reduced cell proliferation, migration and invasion potential, and tumor sphere formation. Cell cycle analysis indicated that miR-106b inhibition induced G1 arrest and apoptosis. The cell cycle regulators, p21 and cyclin D1, and apoptotic marker cleaved PARP were differentially expressed in miR-106b inhibitor-transfected cells. PTEN was identified as a direct target gene of miR-106b. Luciferase reporter assay confirmed miR-106b directly interacted with the 3′UTR of PTEN. We found miR-106b directly targeted PTEN at transcriptional and translational levels. Immunohistochemistry revealed a trend between MAPK Inhibitor Library cell assay PTEN and miR-106b in MB tumors (p=0.07). These data suggested the upregulation of miR-106b in MB and the involvement Sirolimus supplier of miR-106b in MB biology. “
“Marinesco bodies (MBs) are spherical eosinophilic intranuclear inclusions in pigmented neurons in the substantia nigra and locus ceruleus. Previous immunohistochemical

studies have shown that MBs are positive for ubiquitin, p62 and SUMO-1, suggesting the involvement of ubiquitination and related proteins in the formation or disaggregation of MBs. However, the involvement is not thoroughly understood. Therefore, we immunohistochemically examined the midbrain from five control subjects ranged from 53 to 84 years old. MBs were positive for various proteins implicated in the ubiquitin-proteasome system (ubiquitin, p62, EDD1, NEDD8, NUB1, SUMO-1 and SUMO-2), aggresome formation (HDAC6)

and autophagy (ubiquitin, p62, LC3, GABARAP and GATE-16). These findings suggest that proteins related to ubiquitination, proteasomal degradation Cepharanthine and autophagy are involved in the formation or disaggregation of MBs. “
“J. A. R. Nicoll, G. M. Savva, J. Stewart, F. E. Matthews, C. Brayne and P. Ince (2011) Neuropathology and Applied Neurobiology37, 285–294 Association between APOE genotype, neuropathology and dementia in the older population of England and Wales Aims: Apolipoprotein E (APOE) genotype is the major genetic risk factor for sporadic Alzheimer’s disease (AD) but it is unclear how this is mediated. Most studies of APOE genotype have used case–control design to compare groups differing by two variables: i.e. dementia and AD pathology, so it is unclear to which of these variables APOE genotype is more strongly related. The prospective Medical Research Council Cognitive Function and Ageing Study neuropathology cohort is population-based sample in which donations are unbiased by dementia status. Methods: We investigated the association between APOE genotypes and neuropathological and cognitive data in this cohort (n = 310).

[18] The reconstitution of the immune system by HAART can lead to

heightened immunity against a variety of pathogens. Indeed, the initiation of HAART has been reported to be associated with the development of RR in co-infected HIV/leprosy patients.[19, 20] Patients with concurrent HIV infection and leprosy who are not receiving HAART did not trigger RR at the same rate as HAART-treated patients, which could be explained by the increase in cellular immune response promoted by this treatment.[21] Patients with HAART-associated RR may present uncommon clinical features such as lesion ulcerations.[14] In fact, several authors have suggested that the initiation of HAART may even accelerate the onset of leprosy symptoms.[17] A clear understanding of RR pathogenesis within the HIV-infected group is required Proteasome inhibitor to investigate the causes of RR and identify exactly which individuals are most at risk so that more specific and effective treatment strategies can be developed. As such, the purpose of the present study was to determine the specificity of the immune response to ML at the onset of RR. Indeed, characterizations of the immune T-cell phenotype were also performed with special

attention to the cellular activation status and memory profile of the CD4+ and CD8+ T cells that may be involved in RR PARP inhibitor co-infected patients in response to ML, including activation and maturation markers. The present study was conducted at the Souza Araújo Outpatient Unit at FIOCRUZ in Rio de Janeiro, RJ, Brazil, and included patients diagnosed between 2008 and 2012. The Souza Araújo Outpatient Unit at FIOCRUZ has been a reference centre for HIV and ML co-infected patients since 1989. All patients followed a routine dermatological and neurological evaluation. Leprosy was diagnosed and classified

according to Ridley–Jopling criteria. The variables under consideration at diagnosis were gender, age, clinical form of the disease, World Health Organization operational classification, bacillary load and time period from HIV diagnosis and initiation of HAART to leprosy diagnosis. The CD4 T-cell count and viral loads were determined at leprosy diagnosis (defined as the first time the patient visited Tobramycin a health centre with signs of leprosy). The study was approved by the Ethics Committee of the Oswaldo Cruz Foundation; and informed consent protocols were signed by each individual before sample collection. Twenty-five individuals (13 males and 12 females) were assessed in the study. Of the total, 10 were HIV/leprosy co-infected patients presenting RR at diagnosis, which represented 47.62% of all co-infected cases diagnosed during the study, 10 were leprosy patients (without HIV co-infection) who experienced RR during leprosy treatment, and five were healthy individuals (HC). All patients received multidrug therapy as recommended by the Brazilian Ministry of Health.

This could be due to the binding R788 molecular weight of NKp46 mAbs used for sorting and which increased the degranulation of NK cells compared with negatively sorted NK-cell subsets (data not shown). However, we did not detect “all-or-none” responses in the two murine NK-cell subsets.

NK cells from all subsets have overlapping functional characteristics, and it was reported in humans and mice that, e.g. IFN-γ production can change over a short period of time 29, 30. This demonstrates the variability of NK-cell functions. In conclusion, our data suggest the applicability of the surface marker CXCR3 for a better discrimination of murine NK-cell subsets resembling those in humans. Characteristics of the discussed NK-cell subsets are summarized in Fig. 7. This will form the basis for in vivo analyses of defined NK-cell subsets in animal models. The differential coexpression patterns of markers such as CXCR3 and CD27 on NK cells enables a more detailed characterization of NK-cell populations and indicates that the entire NK-cell compartment is composed of more than just the two subsets, which have been the focus of recent NK-cell research. For all experiments, 8–16 wk-old female C57BL/6 mice

(Charles River Laboratories, Wilmongton, Temsirolimus MA, USA and animal facility Hannover Medical School, Hannover, Germany) were used. Mice were bred under specific pathogen-free conditions and maintained in filter-topped cages under conventional conditions. Experiments involving animals were performed in compliance with federal and institutional guidelines (according to FELASA). Peripheral blood was taken from the retro orbital plexus and collected into heparinized tubes. White blood cells were prepared by hypotonic lysis of red blood cells (RBC lysis buffer, containing

NH4Cl) and washed in PBS containing 3% FCS (PAA Lab, Cölbe, Germany). Mice were PIK3C2G euthanized by CO2 asphyxiation or cervical dislocation. Organs (LN, spleen, uterus, thymus, liver and lung) were extracted, sliced and homogenized with a 40 μm nylon (BD Pharmingen, Heidelberg, Germany) or steel mesh. For isolation of BM cells, femurs and tibiae were flushed with PBS using a 27G syringe. When necessary, cell suspensions were enriched for lymphocytes via density gradient (Lympholyte M, Cedarlane, ON, Canada) or treated with red blood cell lysis buffer (0.146 M NH4Cl, 0.1 mM EDTA-Na2, 1g NaHCO3, pH 7.3). The mouse-specific mAb Ly49D (4E5, FITC), Ly49G2 (4D11, FITC), Ly49C/I (5E6, FITC), NK1.1 (PK136, FITC, PE, APC), CD3 (145-2C11, FITC, PE, PerCP), CD16 (2.4G2, PE), CD27 (LG.3A10, PE), CD45 (30-F11, FITC, PerCP), CD107a (1D4B, FITC), CD122 (TM-β1, PE) and IFN-γ (XMG1.2, PE) were purchased from BD Biosciences (Heidelberg, Germany). In addition, the following mAb were used: CD3 (145-2C11, AlexaFluor® 647), CD27 (LG.3A10, PerCP/Cy5.5, Biolegend, San Diego, CA, USA), CD11b (M1/70.

Briefly, the DE52-purified parasites were resuspended in

Balts-buffer (50 mM sodium phosphate buffer, pH 5.5) and incubation on ice for 30 min followed by a 5-min incubation at 37°C. The solution was subsequently centrifuged (1400 rpm, 7 min, 4°C) and the supernatant treated with benzonase (VWR) to remove potential DNA/RNA contamination this website (as described by the supplier). The supernatant was dialyzed against 10 mM Tris, pH 7.4, and the sVSG was purified using ion-exchange chromatography and gel filtration as described previously 79, 80. mfVSG was prepared as described previously 81. Prior to performing a size exclusion chromatography (equilibrated against 10 mM Tris, pH 7.4, containing 0.02% N-octylglucoside, Sigma-Aldrich), the mfVSG was treated with benzonase (similar as for sVSG) to remove potential nucleic acid contamination. The protein concentration of both VSGs was estimated spectrofotometrically by a detergent-compatible protein assay kit (Bio-Rad) using BSA as a standard. The purity of both sVSG and mfVSG was checked in SDS-PAGE and found to be >95%. In addition, Western blot analysis, using rabbit polyclonal anti-VSG and anti-cross-reacting determinant Abs confirmed the presence of the GPI anchor on mfVSG 82. Finally, the endotoxin levels were determined using the Limulus amebocyte lysate (LAL) test (Cambrex) according to the manufacturers’ instructions and found to be <0.5 pg/μg VSG. BM-DCs were generated as

described previously 83.

Briefly, BM-precursor cells were isolated from the hind limbs and seeded out in petri dishes (10 cm, Greiner) at 3×106 cells per dish. For microarray analysis, BM-precursor Cell Cycle inhibitor cells were depleted of B and T cells by using anti-CD19 and anti-CD90 magnetic beads (Miltenyi Biotec), respectively. Cells were cultured in RPMI 1640 (PAA) supplemented with 10% heat-inactivated fetal calf serum (FCS, Chlormezanone PAA), penicillin (100 U/mL; PAA), streptomycin (100 mg/mL; PAA), L-glutamine (2 mM; PAA) and β-mercaptoethanol (50 mM; Sigma-Aldrich). Culture medium was additionally supplemented with 10% supernatant from a GM-CSF-transfected cell line 84. At d7 or d8, BM-derived DCs were harvested and replated at a density of 106 cells/mL in a 24-well plate (nontissue culture treated; Greiner). For maturation analysis of cytokine production and surface marker expression, BM-DCs were cultured for 20–24 h in the presence of TNF (500 U/mL; PeproTech), LPS (Escherichia coli 0127:B8 0.1 μg/mL; Sigma-Aldrich), sVSG or mfVSG from clone AnTat1.1 (2 μg/mL), or sVSG MiTat1.5 (2 μg/mL). For in vivo polarization assays, BM-DCs were seeded at a density of up to 5×106 cells/mL, matured for 4 h only with different maturation stimuli and additionally loaded with 40 μg/mL MOG35–55-peptide (synthesized and HPLC purified by R. Volkmer, Charité, Berlin, Germany), 10 μM OVA-peptide327–339 (Activotec) or 50–100 μg/mL OVA protein (endotoxin-free; Hyglos) as indicated.

[5, 7] At the same time that urodynamics is recognized

as the most proper tool to evaluate voiding dysfunctions, training on it was deemed insufficient in many surveyed academic centers with almost 50% of the doctors referring to the training as inadequate or insufficient.[6, 8] Alarmingly, in the US only 20% of residents could recall formal training of the exam.[9] A minimum of 30 exams per year was recommended by Minimum Standards for Urodynamic practice in the UK but it is not evidence-based. Our fellowship provides a remarkably higher number enabling the fellows to experience intense exposure Aurora Kinase inhibitor that may change the conceptualization on the use of this tool to appropriately treat BPH patients.[10] Our study analyzed two groups of urologists with different MK-2206 in vivo times of exposition to urodynamic studies and both significantly improved their capacity in doing, interpreting and understanding the importance of the exam as a unique tool to evaluate voiding dysfunctions. As in other surveys, we demonstrated that urodynamic usage for BPH is related to the availability of the exam as well as the reliance on the person performing the test. As in the survey from Canada utilization of urodynamic test prior

to stress urinary incontinence (SUI) operations was related to the availability of the testing in the city or evaluated surgeon’s hospital, meaning that 54% of the surgeons would always Methocarbamol demand the exam but only 5% of the gynecologists who do not readily have it.[11] In the same manner, a multi-institutional study showed that many gynecologists do not use urodynamic investigations as plainly recognized with higher rates of utilization for subspecialists (72% using cystometries against 44% of general gynecologists) despite having easy access to the test. These observations may be related to the lack of recognition on the importance of urodynamic evaluation in prognostic results as well as poor understanding of the information derived from the test.[12] Our data also suggests that senior

urologists are more prone to disregard the results depending on who did the exam adding another factor of incredulity to the reasons doctors disregard the exam. However, our study showed that after being exposed to the urodynamic concepts, 90% of the professionals would order the exam for all patients considered to TURP, translating the recognition of the importance of the exam for further urological treatment in opposition to the Canadian survey that revealed that 91% of the urologists would never or rarely do urodyamics for HBP, with 69% of them doing TURP based solely on symptoms.[3] In the same way, it was astonishing that many urologists still perform cystoscopy more often than urodynamics for voiding dysfunctions as demonstrated in a regional US survey.

This shift is further influenced by changes in acid-base status, osmolality, glucose and insulin concentration and catecholamine activity. The rapid decline in plasma potassium concentration, which occurs in the early stages of dialysis, unfavourably alters the QT interval (a marker of ventricular recovery time) and increases the risk of arrhythmias.10 Redaelli et al.11 demonstrated that modelling dialysate potassium so as to maintain a constant Lumacaftor nmr blood-to-dialysate potassium gradient of 1.5 mmol/L throughout dialysis decreased premature ventricular ectopy, particularly during

the first hour of the dialysis. Hypokalaemia increases vascular resistance and has been implicated in post-dialysis rebound hypertension. Dolson

et al.12 demonstrated a greater incidence of post-dialysis hypertension in patients dialysed against a dialysate potassium of 1 mmol/L compared with 3 mmol/L. Current evidence suggests modelled or higher dialysate potassium should be considered in patients with underlying cardiac disease (particularly those prone to arrhythmias) and those troubled by post-dialysis rebound hypertension. Calcium is central to contraction of vascular and cardiac smooth muscle. Increased serum calcium levels in haemodialysis patients have been associated with greater all-cause and cardiovascular mortality risk, as well as with poor mental health.13 The prescription of dialysate calcium needs to take into account the effects click here of calcium on both the skeleton and the vasculature. There are advantages and disadvantages to both lower and higher dialysate calcium (Table 1). Lower dialysate calcium allows for increased doses

of both calcium-based phosphate binders and vitamin D, with consequent suppression of parathyroid hormone (PTH). However, as demonstrated by Argiles et al.,15 dialysate calcium less than 1.25 mmol/L may result in negative calcium balance and subsequent O-methylated flavonoid stimulation of PTH. The same study showed a reversal of this hyperparathyroidism when patients were subsequently treated with vitamin D. Another disadvantage of lower dialysate calcium is an increased incidence of intradialytic hypotension and decreased stroke volume.16 Thus, low dialysate calcium should be avoided in patients prone to intradialytic hypotension. Severi et al.17 demonstrated that a lower dialysate calcium (resulting in negative calcium balance) when accompanied by end-dialysis hypokalaemia predicted critical QTc prolongation. This suggests that this combination should be avoided, at least in patients with cardiac disease. Kyriazis et al.18 compared 18 patients on low (1.25 mmol/L), medium (1.5 mmol/L) or modelled dialysate calcium (1.25 mmol/L during the first 2 h, then 1.75 mmol/L during the last 2 h). Intradialytic hypotensive events were reduced only with modelled calcium dialysate (See Fig. 1).

Beta-glucan, which is absent in animal cells, but is a major component of the fungal cell wall, is an important recognition target [6]. Many check details PRRs, including dectin-1 [7], scavenger receptors [8], and complement receptor 3 [9], are capable of binding β-glucan. The signaling cascade triggered by interactions between particulate glucan and dectin-1 involves the sequential activation of spleen tyrosine kinase (Syk), CARD9,

and of the NF-κB and NFAT transcription factors. This pathway leads to phagocytosis, the “respiratory burst”, and cytokine gene induction. The importance of this pathway in anti-fungal host defenses has been demonstrated in experimental infections [10, 11] and is corroborated by the association between increased susceptibility to fungal infection and mutations in human genes encoding for

CARD9 [12]. The Syk/CARD9 pathway is also targeted by other lectin-type PRRs, such as dectin-2, which recognizes cell-wall mannans [13]. Much attention has been devoted to the ability of fungi to activate Toll-like receptors (TLRs) and to the ability of the latter to cooperate with lectin-type receptors in immune responses [14-16]. TLR engagement triggers signaling cascades involving intracellular GSK1120212 adaptors, such as MyD88 and TRIF, which result in the activation of several transcription factors, including NF-κB and interferon regulatory factors (IRFs). An important role of TLR-mediated recognition in anti-fungal host defenses is suggested by the extreme susceptibility to infection of MyD88-deficient

mice [14, 17-19]. However, the in vivo role of single TLRs is uncertain [4, 5]. Moreover, the fungal PAMPs responsible for TLR stimulation remain largely undefined, although O-linked mannans and phospholipomannan from C. albicans have been proposed as TLR4 [20] and TLR2 [21] ligands, respectively. Anti-fungal defenses crucially rely on the balanced production of two key cytokines, IL-12p70 and IL-23, which display profound differences in the type of responses that they can elicit in cells of the innate and adaptive immune system. For example, IL-12p70 and IL-23 induce the production of IFN-γ and IL-17, respectively, in T cells. It has been suggested that the production of IL-12p70 and IL-23 are reciprocally regulated through the activation Sitaxentan or co-activation of various TLRs and lectin-type receptors [4, 5]. However, little is known of the role of individual TLRs in such activities, especially in the context of infection with whole fungi, as opposed to stimulation with purified, nonfungal PRR agonists. We show here that TLR7-mediated sensing of fungal RNA leads to the production of a number of important cytokines, such as IL-12p70, IL-23, and tumor necrosis factor-alpha (TNF-α). Moreover, TLR7 was required for the induction of IL-12p70, but not IL-23 or TNF-α, in the context of whole yeast stimulation.