It was found that, before 2001, B51+ individuals displayed

significantly lower pVL than the other patients (median: 5150 vs. 18 000 RNA copies/ml, P= 0.048); however thereafter this protective effect waned and disappeared, whereas no changes were observed for any other alleles over time. These results indicate that, at a population level, some HLA alleles have been losing their beneficial effects against HIV disease progression over time, thereby possibly posing a significant challenge for HIV vaccine development. However such detrimental effects 3-deazaneplanocin A clinical trial may be limited to particular HLA class I alleles. HIV-1 is the causative agent for AIDS. Since the discovery of HIV-1 in 1983, although a myriad of studies focusing on the immunopathogenesis of HIV-1 infection have been conducted, a number of questions remained unanswered, hampering development of HIV/AIDS vaccines. As the HIV-1 epidemic has continued, it has become evident that the rate of decline in CD4+ T cells varies considerably between infected people, and that untreated individuals with larger pVL during the asymptomatic phase of infection progress to AIDS more rapidly than those with lower pVL (1, 2). Host genetics, host innate and adaptive immune selleck products responses, and

viral sequence variations have all been suggested as possible factors influencing the level of viremia and disease outcome (3–5). Amongst host genetic factors, HLA class I types are recognized to be the most influential with respect to disease progression (6–9), indicating that the effects of HLA class I molecules on HIV-1 specific CTL responses play a major role in controlling viremia. A number of studies have reported differential impacts of HLA class

I allele expression on the level of the pVL and/or disease outcome: HLA-B27, B51 and B57 are associated with lower pVL and better clinical outcome (7, 10–12), whereas HLA-B*3502/3503 and B53 have a detrimental effect on these parameters (6, 8, 13, 14). However, such studies have been performed either in Western countries, such as the United States (6, 7, 11), or in South Africa (12), where Caucasians and/or Africans dominate over other ethnic groups; accordingly information from Asian countries is largely lacking, although an estimated ioxilan 5.0 million people were living with HIV/AIDS in Asia in 2007, accounting for 15% of the world total (15). Because people living in Asia have distinct patterns of HLA class I profiles, the known associations between HLA class I allele expression and HIV disease outcome may be applicable only to a limited geographical area on the globe. In order to design globally effective HIV vaccines that aim to induce CTL responses restricted by HLA class I molecules, it is crucial to identify the differential ability of HLA class I alleles to control viremia in different parts of the world. Of importance, CTL escape mutations have been shown to accumulate in populations (16, 17), suggesting that we have been losing targeting epitopes.

A topical vaginal microbicide preventing the HIV virus from establishing an infection through the female genital tract could be live saving for young women and other women at risk. With the recent evidence from the Caprisa004 trial showing a 39% reduction in HIV incidence among those using 1% tenofovir gel,7,8 we urgently need to strengthen and broaden the vaginal HIV prevention research by designing and developing more user-friendly formulations (such as vaginal rings) and more effective products, including the design of new chemicals that are not used for the treatment of HIV, thereby limiting the spread

of resistance to drugs that are part of critical combination treatments. Researchers from the Europrise consortium, representing see more 14 projects funded by the European Commission, are now developing combined antiretroviral vaginal gel products, mucosal vaccines, and vaginal ring devices. Each of these new products will need to prove that they are safe and

efficacious through development pathway steps. Safety trials should BVD-523 mw be designed with the utmost care and specifically assess products for maintenance of healthy vaginal ecology and local mucosal immunity. Similarly, oral pre-exposure prophylaxis (PrEP) or an HIV vaccine, applied intramuscularly, nasally, subcutaneously or through any route should not negatively affect the local vaginal milieu. Of equal importance is the assessment of the presence or absence of protective humoral and cellular immunity in response to a vaccine whatever

the route of application. The cellular immunity (HIV-specific CD8 +  T cells) induced by the MRKAd5 HIV-1 gag/pol/nef vaccine in the Step trial did not provide protection from HIV. In this trial, an opportunity Telomerase was missed to evaluate the local mucosal immune responses to gain insight in the vaccine’s failure.9,10 The best way to assess safety and immune responses to products is by sampling the vaginal milieu; studying the local immune system before, during and after use of the products. A proven, well-documented and standardized sampling strategy will provide high quality data to be able to assess both safety and local immune response. The focus of this review is to critically assess the methods used for vaginal sampling in the context of clinical trials for vaginal products, and to highlight areas that need further exploration. At present, a wide range of clinical methods for sampling is used and new methods are being explored.

Moreover, passively transferred IgA mAbs targeted against the major membrane protein α-crystallin reduced bacterial loads and pathologic changes in intranasally and intratracheally infected mice, whereas mAbs against a secreted protein did not 71, 72. These findings underline the necessity of surface location and accessibility

of Ab epitopes to finally confer protective effects. The mechanism by which Abs confer protection in infections with Mycobacterium spp. is still not fully understood. The long-term duration (up to several months) of some of the above experiments suggests that mAbs confer Proteasome inhibition protection and prolonged survival by enhancing cellular immune responses. At least in one study, involvement of FcRs was excluded, as LAM-specific purified F(ab′) fragments also enhanced host survival upon M. tuberculosis infection in mice 70; however, in vitro experiments with M. bovis bacillus Calmette-Guérin (BCG) indicated a much more direct effect as these bacteria were targeted to lysosomes within minutes upon FcR stimulation of the host cell, suggesting a similar FcR signaling-dependent lysosomal targeting mechanism as is seen for Legionella65. Despite a lack of detailed mechanistic insight, promising vaccines using recombinant bacteria expressing M. tuberculosis protein Ags are being designed to enhance M. tuberculosis-specific humoral immunity 73, 74. An FcR-dependent mechanism is likely to be involved

in Ab-mediated protection against the intracellular parasite Toxoplasma gondii. Toxoplasma does not enter the host cell through phagocytosis but uses an active mechanism that is dependent on actin-mediated movement www.selleckchem.com/products/gsk2126458.html of the parasite into the cell forming a modified phagocytic vacuole in which the parasite resides and replicates 75. By mechanisms that are not completely understood to date, this vacuole does not fuse with lysosomes, and therefore acidification of the replicative niche is prevented 76. In contrast to live

Toxoplasma, dead or specific Ab-coated parasites are primarily located in lysosomes and this rerouting has been shown to be dependent on FcRs 76, 77. Once Toxoplasma is located in the lysosomal compartment, Astemizole macrophages are able to kill the parasites and replication can no longer take place 78. As studies using μMT mice showed that Abs also play a crucial role in mediating resistance to Toxoplasma in vivo, it is likely that, as in Legionella infection, Abs are able to activate macrophages via FcRs and convert them to a state where they are no longer permissive for parasite replication 79. Salmonella actively induce their uptake into host cells by using a type III secretion system (T3SS)-1 to inject effector proteins into the cytoplasm. These effectors induce reorganization of the host cell’s actin cytoskeleton, leading to the formation of phagosomes allowing Salmonella to invade phagocytic as well as nonphagocytic cells.

What is not clear is the influence of the different IL-4-producing cells within the lymph node. Do basophils secrete IL-4 multi-directionally and T cells secrete focused IL-4? If IL-4 secretion is representative of other effector cytokine secretions, the former study129 supports the notion that cytokines are only secreted at the site of antigen re-encounter,

spatially separating differentiation from effector function. Whether peptide–MHC complexes are the final or only trigger activating effector Th2 cells in non-lymphoid tissue or if signals with or without TCR engagement can trigger effector function is not clear. The local cytokine environment, including IL-3384 and TSLP,130 can enhance Th2 cytokine secretion, but whether ST2 and TSLP-R ligation also requires TCR engagement is not clear. Furthermore, GDC-0068 supplier the cross-talk between damaged stroma following invasion, tissue damage, or danger signals and their direct impact on selleck Th2 cells has not been reported. The impact and role of Th2-derived cytokines has been widely reported. It is undisputable that IL-4 is required for optimal IgG1 and IgE class switching in B cells,131 alternative activation of macrophages132 and Th2 stability; IL-5 mobilizes, matures133 and recruits eosinophils134 and IL-13 induces goblet cell differentiation, mucus secretion and tissue repair.135 Th2 cells

can certainly provide this trio of potent cytokines, but they are not the only ones. The recently reported type-2 innate-like

cells seem more than capable of fulfilling this role Fenbendazole as cytokine providers but they do not appear to be controlled by antigen specificity. In addition to overlapping cues for the development of Th2 cells, their functional properties may also have overlap and redundancy. For example, infection of IL-5, IL-9 and IL-13 compound cytokine-deficient mice with N. brasiliensis demonstrated the ability of IL-4 to mediate worm expulsion,136 although these mice have not been extensively studied. Nevertheless, intestinal helminth infection models have unanimously identified mechanisms of protection optimally mediated by αβ+ CD4+ Th2 cells activating a suite of innate cells. The inflammatory phenotype seen in Th2-driven asthma is also characterized by the release of IL-4, IL-5, IL-13 and IL-9.137 These features of disease have focused researchers for many years on developing strategies to perturb Th2 development and effector function to benefit allergies and to identify ways of enhancing Th2 functions to protect against helminths, or at least, the intestinal-dwelling helminths. Therapeutic approaches that involve the use of biological modifiers such as monoclonal antibodies that target Th2-associated cytokines are being tested (reviewed in ref. 138). Interestingly, such intervention studies have shown that selective inhibition of IL-4 is not effective for the treatment of asthma.

18 A STAT-5 phosphorylation assay was used to gauge IL-7 responsiveness in CD4+ and CD8+ cells. The increase of the percentage of P-STAT-5 cells, and an example of constitutive P-STAT-5 and IL-7-induced P-STAT-5, in HD and NHP are shown in Fig. 5(a,b). In NHPs, (n = 15) 84·4 ± 10·8% and 60·6 ± 12% of CD4+ and CD8+ cells showed an increase of P-STAT-5 cells in response to IL-7 stimulation. Similar numbers were obtained in PBMCs from HDs (n = 10): 87·6 ± 7·6% and 62·3 ± 15·4% in CD4+ and Barasertib solubility dmso CD8+

cells, respectively. CD4+ and CD8+ subsets showed comparable responses to IL-7 stimulation as measured by STAT-5 phosphorylation in NHPs and HDs. In HDs and NHPs more CD4+ cells than CD8+ cells showed STAT-5 phosphorylation (consistent with higher levels of IL-7Rα expression on CD4+ T cells) but the amplitude (measured by MFI) was not statistically different between CD4+ and CD8+ cells. The presence of regulatory cells was assessed by expression analysis of CD25 and FoxP3 in the CD4+, CD8+ and CD4+ CD8+ T-cell compartments (gating strategy see Supplementary Fig. S2). In NHPs, the

CD4+ T-cell compartment showed the following frequencies: 16·5% (median values) were CD25intermediate (CD25interm.) and 0·5% stained for CD25bright; in CD4+ CD8+ T cells: 19·6% cells were CD25interm. and 1·4% were CD25bright; in CD8+ T cells: 1% were CD25interm. and 0·07% CD25bright (Table 2). Compared with HDs, higher frequencies of CD4+ CD25interm. T cells and CD4+ CD8+ CD25interm./bright,

and CD8+ CD25bright T cells (21%) were detected in PBMCs from NHPs. Analysis selleckchem of FoxP3 expression in the different CD25+/− T-cell compartments showed that the majority of CD25bright T cells in NHPs were FoxP3+ (87·5% of CD4+ and 76% of CD4+ CD8+ and CD8+ T cells), whereas either only 10–20% of CD25interm. T cells showed FoxP3 expression (Fig. 6a). In contrast, almost no FoxP3 expression could be observed in human CD4+ CD8+ CD8+ T cells that exhibited the CD25interm. phenotype. Analysis of PBMCs from four of eight HDs showed that CD4+ CD8+ and CD8+ T cells, which displayed a CD25bright phenotype, stained also positive for FoxP3. In summary, statistically higher frequencies (P ≤ 0·05) of CD4+/− CD25interm.FoxP3+/−, CD4± CD8± CD25interm./high FoxP3+/− and CD8± CD25interm./high FoxP3+/− were detected in NHPs than in HDs. Expression of the IL-7Rα on NHP CD25bright T cells was inversely correlated with expression of FoxP3, which is similar to the situation described in humans.25 More than 90% of NHP CD4+ CD8+ CD25interm./bright FoxP3+ T-cell subsets did not express the IL-7Rα, whereas the majority of CD4+ CD8+ CD25+/− FoxP3− (33–67%) were positive for IL-7Rα (% of IL-7Rα expression is shown for CD4+ T cells in Fig. 6b). The same trend was observed in HDs. However, 9% of human CD4+ CD25bright FoxP3+ T cells expressed the IL-7Rα (Fig. 6b), this was not true for the same T-cell subset in NHPs (3·8%).

Figure 4. Overexpression huBCL-2 and huMCL-1 in CD8αα+ iIELs from WT and Il15ra−/− mice Figure S5. Bcl-2 and Bim affect CD8αα+ iIELs survival during in spleen compartment of Il15ra−/− recipients. Figure S6. IL-15-mediated ERK activation in CD8αα+ iIELs is unlikely stimulated by IL-15-induced secreted soluble factor(s) Figure S7. Working model for IL-15-mediated CD8αα+ iIEL survival “
“Diagnostic tests for tuberculosis (TB) using interferon gamma (IFN-γ) responses produced by T lymphocytes after stimulation by early secretory antigen target 6 (ESAT-6), culture filtrate protein Doxorubicin price 10 (CFP-10) or purified protein derivate (PPD) were carried out using ELISA (enzyme-linked immunosorbent assay) in whole blood culture supernatants

from children with suspected TB disease (n = 21), latent TB infection (LTBI; n = 17) and negative controls (NC; n = 21) from Recife, Pernambuco, Brazil. The results were analysed using the ROC (receiver operating characteristic) curves and the areas under the curve (AUC) generated varied from 0.5 to 1.0 with higher values indicating increased discriminatory ability. Comparisons of AUCs were made using non-parametric assumptions, and the

differences were considered significant if P < 0.05. The ROC curve showed a statistical difference (P = 0.015) between the LTBI and NC groups with an AUC of 0.731, TB disease and NC (AUC = 0.780; P = 0.002) Selleckchem PI3K Inhibitor Library and a group with TB (latent infection + disease, n = 38) and NC (AUC = 0.758; P = 0.001) when the antigen used was ESAT-6. No statistical difference was found between the groups when CFP-10 or PPD was used. In conclusion, the ESAT-6 test may be the most appropriate for diagnosis of childhood TB, both LTBI and TB disease, when associated with epidemiological and clinical data, especially in endemic areas such as Brazil. Tuberculosis (TB) is one of the most important infections of humans and a major Sclareol global public health problem. The World Health Organization (WHO) [1] has annually reported approximately 9.2 million new cases of TB and 1.7 million deaths attributed to this disease. On the other hand, it has been estimated that one-third of

the world population is infected with the intracellular pathogen, Mycobacterium tuberculosis, and one of the most remarkable features of this pathogen is its capacity to generate a latent infection [2, 3]. People that have latent TB infection (LTBI) could be a potential reservoir for future infections, especially when the patient is in childhood and has a compromised immune system [4]. However, depending on the epidemiological situation and the intensity of infection locally, the probability of development of clinical disease after infection with M. tuberculosis may vary [5]. In Brazil, according to the Ministry of Health (2004), 116 000 cases of tuberculosis are reported every year, of which 10% are in children. The country may thus be considered an area where TB is endemic [1].

We analyzed T-cell subpopulations in Pim1TgγcKO LN and spleen, but found that neither γδ T cells, CD25+FoxP3+ Treg-cells, or NKT cells

were recovered (Fig. 5A–C). Also, CD8α+ IELs were drastically reduced and the IL-15-dependent CD8αα IEL population was completely absent (Fig. 5D), suggesting a nonredundant role of γc cytokines in generation and maintenance of these cells. We also failed to observe any γδ T cells in the IEL population (Fig. 5E). Altogether, Pim1 was sufficient to restore peripheral CD4+ αβ T-cell numbers and to improve CD8+ T-cell survival in the absence of γc. However, it was insufficient to restore other T-lineage check details cells, including γδ T cells, NKT cells, CD8αα IELs, and FoxP3+ Treg cells. Thus, CD4+ T cells are unique in that Pim1-mediated survival effect was sufficient to meet their γc signaling requirement. To understand the extent to which Pim1 can replace the γc requirement, we analyzed Pim1TgγcKO LN T cells in further detail. We found that all LN T cells had downregulated IL-7R-α and CD103 expression that resembles

an activated/memory phenotype (Fig. 6A). In agreement, most Pim1TgγcKO CD4+ and CD8+ T cells expressed high levels of the memory marker CD44 (Fig. 6B). Thus, Pim1 promotes T-cell survival in the absence of γc, but it fails to maintain a naïve T-cell pool. Interestingly, surface CD8 buy LY294002 protein levels on Pim1TgγcKO CD8+ T cells were significantly lower than on WT CD8+ T cells (Fig. 6C). Since in vivo CD8 surface and mRNA levels are determined by IL-7 signaling [28], reduced CD8 surface and mRNA levels suggested that Pim1 cannot replace the CD8 regulatory arm of γc signaling (Fig. 6C and Supporting Information Fig. 3D). Along this line, we found that expression of the CD8 lineage specifying factor Runx3, but not Runx1, was significantly reduced in Pim1TgγcKO CD8+ T cells (Supporting Information Fig. 3D). Taken together, these data indicate that Pim1 is limited in its ability to replace in vivo effects of γc signaling, and that additional γc signaling pathways are necessary to maintain CD8+ T-cell homeostasis. To test whether γc signaling is

required for Th function, next we analyzed surface CD40L expression on activated Pim1TgγcKO CD4+ T cells. Tolmetin Overnight TCR stimulation upregulated CD5 and CD40L expression on both WT and Pim1TgγcKO CD4+ T cells (Fig. 6D). CD40L expression was CD4+ T-cell specific since activated CD8+ T cells failed to express CD40L (Supporting Information Fig. 3E). These results indicate that CD4+ Th function can be acquired in the absence of γc. On the other hand, Th lineage differentiation was dependent on γc signaling. Stimulation of Pim1TgγcKO CD4+ T cells under Th1 or Th2 cell differentiating conditions failed to produce Th1 or Th2 cells based on intracellular IFN-γ and IL-4 expression, respectively (Fig. 6E). However, IL-17a producing Th17-cell differentiation, which is mediated by the non-γc cytokines IL-6 and TGF-β, was intact in Pim1TgγcKO CD4+ T cells (Fig. 6E, bottom).

There is also a significant degree of overlap among the reported diagnostic accuracies of tests. Studies differ in case mix, specific test characteristics and cut-off points of positive

test results, all of which may affect estimates RGFP966 cost of test performance. There are no randomized controlled trials reported in this area. There are three meta-analyses4,12,13 and two prospective comparative studies.14,15 These studies fulfilled the following predefined criteria to allow assessment of comparative test performance: 1 suspected RVHT was the indication These studies form the basis for the formulation of this subtopic. A high quality meta-analysis by Williams et al.13 examined 88 studies involving 9974 arteries in 8147 patients. The data were analysed according to a hierarchical summary receiver-operating

characteristic (ROC) curve model (Tables 1,2). Heterogeneity in test performance relating to population and design features were Androgen Receptor antagonist also investigated. The following four parameters were evaluated – peak systolic velocity (21 studies), acceleration time (13 studies), acceleration index (13 studies) and renal aortic ratio (13 studies). It was concluded that duplex sonography is a moderately accurate test for RAS and that single peak systolic velocity has the highest performance characteristics, with expected sensitivity of 85% and specificity of 92%. Additional measurements did not increase accuracy. The meta-analysis performed by Vasbinder et al.4 included five studies16–20 that met the predefined inclusion criteria. In three studies, the assessment was blinded. Overall sensitivities Cobimetinib and specificities ranged from 94% to

100% and 92–99%, respectively. The area under the ROC curve for CTA was 0.99 (Table 3). The meta-analysis by Tan et al.12 identified 39 studies, of which 25 met inclusion criteria. The number of patients included in the meta-analysis was 998: 499 with non-enhanced MRA and 499 with gadolinium-enhanced MRA. The sensitivity and specificity of non-enhanced MRA were 94% (95% confidence interval (CI): 90–97%) and 85% (95% CI: 82–87%), respectively. For gadolinium-enhanced MRA sensitivity was 97% (95% CI: 93–98%) and specificity was 93% (95% CI: 91–95%). Thus, specificity and positive predictive value were significantly better for gadolinium-enhanced MRA (P < 0.001). Accessory renal arteries were depicted better by gadolinium-enhanced MRA (82%; 95% CI: 75–87%) than non-gadolinium MRA (49%; 95% CI: 42–60%) (P < 0.001). It was concluded that MRA with gadolinium enhancement is highly sensitive and specific for diagnosis of RAS (Table 4). Vasbinder et al.4 in their meta-analysis involving 16 studies on MRA demonstrated that gadolinium-enhanced MRA had the highest diagnostic performance. The area under the summary ROC curve for gadolinium-enhanced MRA was 0.

32 In a simulated age-matching allocation system, the reallocation of donor kidneys ≥ 65 years from younger recipients < 65 years (old-to-young) to older

recipients ≥65 years (old-to-old) would result in a decrease in 10 year graft survival from 21% to 13% (P < 0.001), whereas reallocation of donor kidneys <65 years from recipients ≥65 years (young-to-old) to younger recipients <65 years (young-to-young) would result in an improvement in 10 year graft survival (19–26%, P = 0.40). In this study, there was 3-deazaneplanocin A ic50 no net benefit of implementing an old-for-old allocation system with regards to overall functional graft years (Table 2). In Australia, the utilization of older donors has steadily grown over the years, with donors aged ≥55 years increasing from 134 in 2001–2003 to 241 in 2007–2009 (i.e. an increase from 12% to 34% of overall donors).7 We have previously reported a simulated age-matching allocation system and its impact on graft outcomes. Using the Cetuximab ANZDATA registry database, we compared total functioning graft years of current deceased donor allocation system with a model based on age-matching.31 Of the 4616

renal transplant recipients between 1991 and 2006, 70% were aged <55 years at time of transplantation. Consistent with other studies, we found that recipients ≥55 years had more than a 2.5-fold increase in death with functioning graft compared with recipients <55 years (HR 2.84, 95% CI 1.97, 4.10 for 0–1 year; HR 2.78, 95% CI 2.19, 3.53 for 1–8 years and HR 4.44, 95% CI 3.10, 6.35 for >8 years; all P-values < 0.01) (Fig. 1). Risk of early (<1 year) and late (>8 years) death-censored graft failure

was similar in recipients aged <55 years and ≥55 years. Grafts from donors ≥60 years were associated with a >50% increased risk of death censored graft failure and death with functioning graft, for the period between 1 and 8 years post-transplant. Older recipients had lower rates of rejection, which may partially explain the better creatinine at 1 and 5 years. ioxilan In contrast, grafts from older donors were associated with a significant increase in mean serum creatinine at 1 and 5 years, with a greater negative impact on renal function in younger compared with older recipients (young recipient/old donor pairs +37 µmol/L and +38 µmol/L at 1 and 5 years post-transplant compared with old recipient/old donor pairs +18 µmol/L and +26 µmol/L at 1 and 5 years post-transplant; reference group young recipient/young donor pairs). The application of an age-matching allocation model to the same cohort of 4616 transplants, whereby all younger donor kidneys were allocated to younger recipients and older donor kidneys were allocated to older recipients would result in an additional 262 mean functioning graft years, which would equate to $11.8–21.7 million savings in dialysis cost (cost per patient per year on dialysis $45 000–83 000).

Previously, our group verified higher activity of mannose receptors on Selleck Ku 0059436 macrophages from mice

pretreated with Con-A for 3 days compared to control group (Geraldino et al., 2010). In that study, Con-A-activated cells were able to destroy 70% of the C. albicans CR15 inoculum during 1 h of coincubation; however, macrophages from the control group killed only 30% of the pathogen. In this study, a reduction of 50.1 ± 3.6% in Candida phagocytosis was observed in the presence of mannan (100 μg mL−1) and 40.2 ± 3.8% in the presence of laminarin (100 μg mL−1), revealing higher activity of mannose and dectin-1 receptors on Con-A-activated macrophages, but not in PBS-macrophages (Table 1). Owing to the increase in the activity of mannose and dectin-1 receptors,

in this study, it was proposed that these pathways of phagocytosis could be mediating an adaptative immune response involving TH17 cells over the course of mouse infection with Candida. In the Con-A group, a significant increase in IL-17 concentrations occurred at 6 h postinfection that was maintained up to 18 h (Fig. 1). In the control group, analysis verified that the levels of IL-17 were significantly reduced over the course of infection compared to mice pretreated with Con-A (Fig. 1). Therefore, this study demonstrated the possibility that mannose and dectin-1 receptors could signalize click here the differentiation of TH17 cells with IL-17 production in the course of Candida infection in mice pretreated with Con-A. Corroborating these results, Van de Veerdonk et al. (2009) and LeibundGut-Landmann et al. (2007), reported that mannose receptors on human macrophages and dectin-1-activated dendritic cells from mice participate in the differentiation of naïve TCD4+ in effector T cells (TH-17 cells) in vitro in response to C. albicans. Although numerous studies have focused on the pathological aspects of IL-17-producing cells in autoimmune diseases, their role in protective antifungal immunity has also been increasingly Adenosine triphosphate recognized (Conti & Gaffen, 2010;

Rehaume et al., 2010). Thus, our interest was to investigate whether the cytokines TGF-β, IL-1β and IL-6 could be driving the development of TH17 cells. Figure 2a shows basal levels of TGF-β in both groups; however, the levels of this cytokine were significantly higher in mice pretreated with Con-A 2 h postinfection, suggesting a trigger for TH17 differentiation. Corroborating these results, Mangan et al. (2006) demonstrated that TGF-β acted to promote a substantial increase in TH17+ cells independent of IL-23 in an experimental model under IFN-γ-null conditions; furthermore, the development of TH17 cells was impaired in TGF-β1-deficient mice, and also, IL-17 secretion was impaired in a dose-dependent manner when neutralizing antibody to TGF-β or IL-6 were present (Torchinsky et al., 2009). IL-6 production is dependent on signaling by dectin-1 receptor according to LeibundGut-Landmann et al.