65–67 In an epidemiological study, Rohrmann et al. reported that men with metabolic syndrome had an increased risk of nocturia, incomplete bladder emptying, weak stream

and hesitancy.68 Yu et al. indicated that hyperlipidemia is associated with OAB in Taiwanese women.69 Furthermore, obesity alone or combing with diabetes can precipitate BAY 80-6946 order lower urinary tract dysfunction, such as OAB and stress urinary incontinence in women.70 The impact of diabetes on the lower urinary tract is multifactorial, including osmolarity diuresis effect, metabolic perturbation, and neuropathy. Diabetes may cause dysfunctions of smooth muscle, urothelium and neuronal components of the bladder.71,72 In a survey of 1359 consecutive DM subjects, 22.5% reported having OAB with 11.7% reporting OAB dry and 10.8% with OAB wet.73 The male gender (24.8%) was more commonly associated with OAB than female gender (20.1%) in DM population with a mean age of 60 years.73 Diabetic men had a larger prostate than the non-diabetic group.74 Men aged 60 years or above had a high prevalence of benign prostatic hyperplasia, which often caused BOO and contributed to the presence OAB. The impact of diabetes on bladder function was observed in a model of streptozocin-induced diabetic rats. In the early stage of diabetic bladder dysfunction, remodeling of the bladder wall occurs.75,76The

diuresis and metabolic effects of diabetes result in detrusor hypertrophy and mechanical property changes, which Edoxaban cause a decrease in bladder voiding efficiency. The early stage of diabetic vesical neuropathy also contributes to the development of detrusor

overactivity. Increased expression www.selleckchem.com/products/pci-32765.html of M2 and M3 receptors in uroepithelium and bladder muscle layer were observed in 2-week-old streptozocin-induced diabetic rats.77,78 However, in patients with classic diabetic cystopathy, decreased bladder sensation and urodynamic detrusor underactivity are seen and may explain why some patients with diabetic bladder dysfunction can have reduced urgency. In an animal model of metabolic syndrome induced by fructose feeding, Tong et al. reported that upregulation of M2,3-muscarinic receptors in the bladder were associated with DO.79 The metabolic perturbations induced by long-term fructose feeding also contributed to DO and OAB symptoms, including proinflammation, increased oxidative stress, mitochondria dysfunction, an increase of apoptosis in the detrusor muscle, and detrusor hypertrophy.80,81 In a spontaneously hypertensive and hyperlipidemic rat model, Nobe et al. also indicated decreased Rho kinase and protein kinase activities, which weaken detrusor contractility.82 It has been shown that heritable hyperlipidemia can cause reduced bladder capacity, DO and nerve degeneration in a chronic hyperlipidemic rabbit model.83 This observation may explain the increase of OAB symptoms in patients with hyperlipidemia.70 Azadoi et al.

As surprising as it may appear, the presence of bacteria in the gut lumen contributes to the integrity of the intestinal epithelial barrier [26]. This is achieved by a series of molecular events induced

by the gut microbiocenosis. One event is increased synthesis of pIgR (epithelial polymeric immunoglobulin receptor), which provides the translocation of sIgA (secretory IgA) Selleck Cabozantinib from LP in the intestinal lumen [27] (Fig. 1). sIgA, a valuable local defence tool, prevents unwanted antigens from adhering to the intestinal mucosa. pIgR-deficient mice that lack sIgA and sIgM exhibit an altered barrier function of the intestinal epithelium, but are also more prone to gaining oral tolerance [28]. This argues for a dual function of a competent intestinal mucosa, ensuring both protection against harmful agents and acceptance of small amounts of certain antigens which induce the development of Tregs. Another event triggered by some species of commensal bacteria is the abrogation of polyubiquitination, necessary for IκB-α degradation [29]. IκB-α is the molecule that controls the activity of nuclear factor (NF)-κB, acting as its suppressor. IκB-α degradation is dependent on both phosphorilation and polyubiquitination. A longer life of IκB-α due to suppressed polyubiquitination will result in reduced MK-2206 research buy proinflammatory activity of NF-κB. The barrier function of the enterocytes is completed by anti-microbial peptides (AMP)

and mucin proteins production [30]. We must specify that AMPs are produced mainly by Paneth cells, and intestinal mucus is the major result of goblet cell activity. Enterocytes produce mucin proteins, which compose the glycocalix, and anti-microbial factors such as β-defensins and hepatocarcinoma–intestine–pancreas/pancreatitis-associated protein (HIP/PAP) [31]. β-defensins bind to the microbial cell membrane and, once embedded, form pore-like membrane defects that allow efflux of ions and nutrients. HIP/PAP is a member of the C-type lectin family and has a promising potential for ID-8 tissue regeneration and protection against apoptosis and cellular stress, being already tested as an agent for the therapy of acute

liver failure in humans [32]. Human β-defensin-1 (HBD-1) is expressed constitutively in enterocytes, while HBD-2 and HBD-3 are induced by microbial products and inflammatory cytokines [33,34]. Inducible expression of HBD-2 and HIP/PAP proteins in enterocytes was shown to be influenced by Toll-like receptor (TLR)- or myeloid differentiation primary response gene 88 (MyD88)-dependent signalling [35,36]. β-defensins may also chemoattract immature DCs [37] and have direct effects on DC function by inducing up-regulation of co-stimulatory molecules and DC maturation [38]. Enterocytes possess specialized receptors of the pathogen recognition receptors (PRR) family, such as TLRs and nucleotide oligomerization domain (NOD)-like receptors.

In experimental models

of immune activation, Tem cells constitutively express CD40L at levels sufficient to induce DC activation in an antigen-independent manner 17. The CD40/CD40L axis is crucial for DC maturation and the subsequent T-cell priming. However in the tumor microenvironment this costimulatory pathway is often dampened, thus impairing the generation of an efficient anti-tumor immune response 18, 19. In this study we have investigated the mechanisms by which OX86 modulates Treg- and Teff-cell functions and their reciprocal interactions with DCs at the tumor site. We propose a model of the tumor microenvironment in which, after OX86 treatment, DCs receive a lower IL-10-mediated inhibition by Treg selleckchem cells on the one hand, and a stronger stimulation from Tem cells, via the CD40/CD40L axis, on the other. In this favorable condition, DCs acquire a stronger migratory ability toward the draining LNs (dLNs), thus inducing a specific anti-tumor immune response. Intratumoral OX40 triggering promotes tumor rejection modulating both Treg- and Teff-cell functions 3, through unknown mechanisms. Here, we separately analyzed the consequences of OX40 triggering on Treg and Teff cells. Treg cells infiltrating the transplantable CT26 colon

carcinoma expressed OX40 at higher levels than Treg cells in dLNs (Fig. 1A). We evaluated IL-10 secretion as part of the Treg-cell-suppressive activity directly ex vivo. Low levels of IL-10 were produced by Treg cells in dLNs (Fig. 1B and C), whereas about 40% of tumor-infiltrating Treg cells spontaneously produced IL-10 (Fig. 1D and E). ATR inhibitor Twenty-four hours after OX86 treatment, IL-10 secretion by tumor-infiltrating Treg cells was significantly decreased (Fig. 1D and E). Similar

results were obtained also in mice bearing TSA mammary carcinoma (Supporting Information Fig. 1). Some authors have reported tumor-infiltrating CD11b+CD11c+ cells expressing OX40 20, while others did not detect OX40 expression on CD11b+ cells, even if OX86 systemic administration could indirectly reduce their frequency in tumors 21. Tumor-infiltrating macrophages (CD45+CD11b+F4/80+), Niclosamide representing the vast majority of immune infiltration in our tumor model, neither expressed OX40 nor was their IL-10 secretion affected by OX40 stimulation (data not shown). The decreased IL-10 production by Treg cells upon OX40 engagement was confirmed with a different experimental approach. BM chimeras were generated such as to carry an IL-10-GFP reporter transgene 22 in the hemopoietic lineage. IL-10-GFP expression, evaluated in tumor-infiltrating CD4+CD25high Treg cells, was significantly reduced after intratumoral OX86 injection (Fig. 1F and G). Unfortunately, we could not finely locate IL-10-GFP expression into the Foxp3+-gated Treg-cell subset, since the fixation step required for Foxp3 detection led to GFP loss (data not shown).

Many of the data that are available are flawed by confounding from significant changes in serum PTH,

which in itself has been implicated in the pathogenesis of CKD cardiovascular disease, and has been performed in the ESKD population, when arguably more benefit could be derived from treatment in earlier stages of CKD. Many questions remain unanswered, including the CKD stages in which intervention is beneficial, which form of vitamin D should be administered and what treatment targets should be recommended to achieve maximal pleiotropic efficacy. The authors would like to thank Mr Andrew Hiscox for the design and production of all illustrations. WP has received scholarships from the University of Queensland, the Centre for Clinical Research Excellence Trichostatin A – Cardiovascular Disease and Metabolic Vincristine Disorders at University of Queensland, and the Department

of Nephrology, Princess Alexandra Hospital. WP has also received peer-reviewed research funding from Roche Pharmaceuticals Pty. DJ Is the recipient of a Queensland Government Health Research Fellowship. “
“We report the successful management of BK virus nephropathy (BKVN) using therapeutic drug monitoring (TDM) of mycophenolic acid (MPA). A 40-year-old woman was admitted for a protocol biopsy 3 months following primary kidney transplantation. Histological features were distributed in mainly two sections: the corticomedullary junction and cortical area. In the former, massive interstitial mononuclear cell infiltration and mild to moderate tubulitis with nuclear inclusion bodies were found. SV40 staining was positive in the injured tubules. These findings were compatible with BKVN. In the latter, focal interstitial inflammation and severe tubulitis without cytopathic changes were identified outside of SV40-positive areas. Based on the histological findings, Thalidomide we diagnosed BKVN and we also suspected of the complication with acute T-cell-mediated

rejection. We started steroid pulse therapy and reduced the dosage of immunosuppressive therapy under careful monitoring, using not only a trough level of tacrolimus but also a 12-h area under the curve (AUC0–12) of MPA. After the treatment, the patient maintained kidney function. This case report demonstrates the usefulness of MPA AUC0–12 for more accurate adjustment of immunosuppressive therapy and the difficulty of pathological differentiation of BKVN and acute cellular rejection. Since the establishment of immunosuppressive therapy, the survival of kidney allografts has improved dramatically; however, the risk of viral infection has increased. BK virus infection is the most common infection after kidney transplantation. Approximately 30–50% of recipients demonstrate viruria by cytology or polymerase chain reaction in the first 3 months, 10–15% progress to viraemia, and BK virus nephropathy (BKVN) develops in 1–10%, leading to graft loss in ∼20%.

The gels were either stained with silver staining or proteins were transferred to polyvinylidene fluoride (PVDF) membrane. The blots prepared from the immunoprecipitates MK-2206 order were

then probed using anti-pSyk antibodies and blots were developed using Millipore chemiluminscent substrate. After Western analysis, blots were stained with Coommasie blue R250 to ensure uniform protein loading. A total of 0·5 × 106 cells were treated with various stimuli and washed with cold PBS; cells were then fixed in 3% formaldehyde for 15 min at RT. Fixed cells were then permeabilized using 95% methanol for 30 min on ice and 10 min at −20°C. After washing, blocking was performed with 1% serum albumin (BSA) and 2·5% species-specific serum diluted in PBS at RT for 1 h. These cells were incubated further with the appropriate primary antibody at a dilution of 1 : 100 for 1 h at RT. For co-staining, a monoclonal antibody recognizing the FcγRIIIA/B and a rabbit polyclonal recognizing the pSyk was used

for staining. Subsequently cells were incubated with AlexaFluor® Small molecule library supplier 488- and 594-conjugated secondary anti-mouse and anti-rabbit at a dilution of 1 : 200 at RT for 1 h. Co-localization for FcγRIIIA/B with pSyk was carried out using Olympus FV-1000 software. Cells were examined from three fields in three experiments in all co-localization studies. Cells were examined at ×400 and ×630 magnification in fluorescent (Leica, DM400B) or confocal microscope (Olympus, FV-1000). In certain cases optical zoom was employed to gain access to cellular details. The Isotretinoin staining for co-localization of FcγRIIIA/B and intracellular FcRγ chain was essentially carried out as described in the earlier section. All serial Z-series sections were included for the analysis (Olympus FV-1000, co-localization software). To co-localize the FcγRIIIA/B, FcγRIIIB with ICs or AHG, a 5 µg/ml of AlexaFlour 488–AHG was used prior to staining of cells with anti-FcγRIIIA/B monoclonal and/or anti-FcγRIIIB antibody. Percentage staining was calculated from three independent fields by enumerating total cells, cells stained with

anti-FcγRIIIA/B and anti-FcγRIIIB. Activated cells were washed with cold PBS and resuspended in 0·1% BSA–PBS. To 1 × 106 cells, a total of 0·2 µg of CTB conjugated with FITC was added and cells were incubated for 20 min in an ice bath. Thereafter, the cells were fixed and stained for FcγRIIIA/B and mounted using SlowFade Gold anti-fade reagent containing 4′,6-diamidino-2-phenylindole (DAPI) (Molecular Probes, Eugene, OR, USA) or without DAPI when using AlexaFluor® 350 conjugate. RT–PCR was performed on the total cellular RNA using the RNA isolation kit (Agilent Technologies, Santa Clara, CA, USA). Using a total of 200 ng of the RNA, the PCR product was generated using the Access RT–PCR system (Promega, Madison, WI, USA).

This study was supported by Nature Science Foundation of Shandong Province (Grant Number: ZR2010HL038). Science and Technology Development Projects of Jining City (Grant Number: 2012jnjc16). None. “
“Lymphodeleption prior to adoptive transfer of tumor-specific T cells greatly improves the clinical efficacy of adoptive T-cell therapy for patients with advanced melanoma, and increases the therapeutic efficacy of cancer vaccines in animal models. Lymphodepletion reduces competition between lymphocytes, and thus creates check details “space” for enhanced expansion and survival of tumor-specific T cells. Within the lymphodepleted host, Ag-specific T cells still need to compete

with other lymphocytes that undergo lymphopenia-driven proliferation. Herein, we describe the relative capacity of naïve T cells, Treg, and NK cells to undergo lymphopenia-driven proliferation. We found that the major population that underwent lymphopenia-driven proliferation was the CD122+ memory-like T-cell population (CD122+CD8+ Treg), and these Poziotinib manufacturer cells competed with Ag-driven proliferation of melanoma-specific T cells. Removal of CD122+CD8+ Treg resulted in a greater expansion of tumor-specific T cells and tumor infiltration of functional effector/memory T cells. Our results demonstrate the lymphopenia-driven proliferation of CD122+CD8+ Treg in reconstituted lymphodepleted

mice limited the antitumor efficacy of DC vaccination in conjunction with adoptive transfer of tumor-specific T cells. Due in large part to the limited expansion and survival of vaccine-induced tumor Ag-specific T cells, active specific immunotherapy of tumor-bearing hosts with tumor vaccines has generally been ineffective

1. Therefore, a major goal of current T-cell based immunotherapy protocols is to induce a large number of tumor-specific T cells capable of mediating regression of established tumors and maintaining long-term memory to prevent tumor recurrence. Lymphodepletion has been recently demonstrated to facilitate the expansion and survival of therapeutic, adoptively Janus kinase (JAK) transferred in vitro-expanded T cells, which induced tumor regression in patients with melanoma (see review in 2). Concurrently, we and others have demonstrated that vaccination induced a dramatic expansion of tumor-specific T cells, and improved the efficacy of active immunotherapy in reconstituted lymphodepleted mice 3–7. While lymphopenic conditioning has been shown to benefit antitumor immunity, and aids in the establishment of the T-cell repertoire in neonatal mice 8, it was detrimental for transplant tolerance 9, and precipitated the development of autoimmune disease 10. Homeostatic proliferation, or more precisely, lymphopenia-driven proliferation of lymphocytes in irradiated or lymphocyte-deficient mice, is a well-studied phenomenon (see review 11).

Therefore, the co-evolutionary trajectories between hosts and pathogens are likely to be species-specific and difficult to forecast in the absence of detailed information on the interactions between the host immune response and parasite growth and transmission. Similarly, parasites that produce both transmissible and nontransmissible stages might elicit different immune protection, with specific effectors targeting the transmissible stages, with a major impact on parasite fitness. In some instances, self-harm might even represent Selleckchem Barasertib a host

defence that reduces the amount of resources that are available to the parasite, as recently suggested for the destruction of noninfected red blood cells in mice infected with Plasmodium chabaudi [79]. A fascinating but still poorly studied phenomenon deals with the evolutionary consequences of the parasite manipulation of the host immune response [1, 80]. As mentioned above, pathogens might adaptively exacerbate the inflammatory response

this website for their own spread and persistence; however, more commonly, parasites aim at down-regulating and evading the host immune response [81]. Interestingly, some pathogens can do both. Mycoplasma initially up-regulates the inflammatory response, and the associated break down of the epithelial cell layer facilitates the spread of the bacterium [82]. Later on, the infection induces a down-regulation of T-cell activity [83]. Similarly, a rodent malaria species (Plasmodium yoelii) has been shown to up-regulate regulatory T Carbachol cells [84]. The evolutionary consequences of immune evasion can be far reaching for both parasite virulence and host defences. Immune evasion mechanisms are often responsible for the pathogenesis of the infection [85], and life history theory tells us that parasite fitness is more sensitive

to mechanisms that avoid early clearance even if they induce a later cost to the host [86]. The study of the intertwined connections between parasite manipulation of the immune system, virulence and host defences is still in its infancy. At the moment, we ignore for instance if immune evasion strategies are genetically variable (but see [87]) and how hosts can neutralize subverted immune functions. Interestingly, the evolution of house finches in response to the Mycoplasma epidemics suggests that resistance has arisen by escaping the bacterium-induced sabotage of the immune system. This work is supported by the Agence Nationale de la Recherche (ANR), the Région Bourgogne and the CNRS (program MIE).

This “outside-in” signaling pathway requires ITAM signals from DAP12 and FcRγ, and also involves early effectors such as the Src family kinases and Syk in neutrophils and macrophages [14, 15]. Because β2 integrins signal through

ITAM adapters in myeloid cells, we hypothesized that β2 integrin signaling may also inhibit TLR responses. There have been conflicting reports in the literature regarding the influence of β2 integrin signaling on TLRs, with some studies demonstrating that β2 integrins can promote TLR-induced inflammation [16-18], whereas others have reported negative roles for these integrins in TLR responses [19, 20]. Therefore, the nature in which β2 integrins interface with TLR activation and cytokine secretion is complex LDE225 cost and unclear.

To better define the contribution of β2 integrins to regulation of TLR signaling, we have examined inflammatory responses in the absence of all β2 integrins. Here we demonstrate that deletion of all β2 integrins rendered myeloid cells hypersensitive to TLR stimulation in vitro and in vivo, showing an inhibitory role for β2 integrins in TLR responses. Furthermore, learn more we examined potential direct and indirect mechanisms by which β2 integrins caused this inhibition, and found that β2 integrins have a direct effect on IκBα degradation that was pronounced in β2 integrin-deficient cells through both early and late phases of TLR stimulation, thus implicating β2 integrin signals in inhibiting NF-κB pathway activation to calibrate inflammatory responses. The four β2 integrins, LFA-1 (lymphocyte function-associated antigen 1, αLβ2), Mac-1 (macrophage-1 antigen, αMβ2), CR4 (αXβ2), and CD11d-CD18 (αDβ2) are heterodimers that consist of distinct CD11 alpha subunits in association with the common

beta chain, CD18 (β2), which is encoded by the Itgb2 gene [21]. To examine whether β2 integrin signaling regulates TLR responses, we compared the cytokine secretion profiles of bone marrow-derived (BM-derived) macrophages from wild-type PRKD3 (WT) and Itgb2−/− mice, which are deficient in CD18 and thus are unable to express any of the β2 integrins on the cell surface (Supporting Information Fig. 1A) [22]. Despite the inability of Itgb2−/− BM-derived macrophages to express Mac-1, these cells exhibited surface F4/80 expression and upregulated MHC II in response to IFN-γ treatment (Supporting Information Fig. 1A and B), demonstrating that they were bona fide macrophages. Furthermore, β2 integrin-deficient macrophages exhibited similar or slightly lower levels of cell surface TLR2, TLR4, and Dectin-1 protein and TLR9 mRNA (Supporting Information Fig. 1C and D). To determine how β2 integrin signals influence TLR activity, we stimulated Itgb2−/− BM-derived macrophages with a panel of TLR agonists, including LPS (TLR4), CpG B DNA (TLR9), and zymosan (TLR2).

Surface Vip (Lmo0320), a bacterial cell wall-anchored protein, also seems to be an important candidate in late stages of the infectious process. Endoplasmic reticulum resident chaperone Gp96 has been identified as a cellular receptor for Vip (Cabanes et al.,

2005). Gp96 is employed in the modulation buy AZD3965 of the immune response by affecting the cellular trafficking of several molecules, including Toll-like receptors. It is predicted that Vip may not only use Gp96 as a receptor for invasion but may also sequester Gp96 to subvert immunological response. Earlier, researchers predicted the induction and thus the involvement of FAK and PI 3-kinase in the Listeria cell invasion as a consequence of Vip–Gp96 binding, as it occurs in E. coli invasion. However, later studies showed Inhibitor Library clinical trial that Listeria interaction with cells does not seem to induce FAK activation for cytoskeletal rearrangements. Similarly, no involvement of the Vip in the increase in tyrosine phosphorylation of protein associated with p85α or Gp96 has been reported elsewhere (Cabanes et al., 2005). Thus, the role of Vip–Gp96 interaction in the Listeria cell entry might be through other signal transduction events associated with Gp96 responses that remain to be elucidated. Another mechanism of BBB translocation, a Trojan horse, needs internalization/phagocytosis of the pathogen by monocytes wherein InlA and InlB play a

crucial role. These internalins and P60 protein bind specific receptors (like

complement Silibinin receptor) on phagocytic cells and trigger the internalization of bacteria through a variety of opsonin-dependent and opsonin-independent mechanisms. Internalization allows persistence in a shielded niche, concealed from circulating antibodies. Listeria, in its intracellular form, stimulates NF-κB and secretion of cytokines IL-1α, IL-1β, IL-6, and TNF-α in phagocytes. Listeria-infected monocytes further upregulate E-selectin, ICAM-1, P-selectin, and VCAM-1, which leads to the adherence to BMECs. The mechanism for this endothelial activation involves listeriolysin O-dependent triggering of NF-κB nuclear translocation in cerebral vessels (Kayal et al., 1999). Infected phagocytes may adhere to endothelium and thus bacteria can invade ECs by cell-to-cell spread in an hly- and actA-dependent process (Greiffenberg et al., 1998; Drevets, 1999). Infected phagocytes then cross the endothelial barrier, and infection can spread to the brain parenchyma cells or subarachnoid space and ventricles (Drevets & Leenen, 2000). As an alternative to adhering to and infecting the endothelium, infected phagocytes could transmigrate and enter the brain tissue. In this case, bacteria contained within phagocytes could spread to cells such as neurons and microglia (Dramsi et al., 1998). Interestingly, pneumococcus, meningococcus, and H. influenzae adhere to the BMECs via 37/67-kDa laminin receptor (LR).

Conflict of interest: The authors declare no financial or commercial conflict of interest. “
“Despite convincing evidence for involvement of members of the Toll-like receptor (TLR) family in fungal recognition, little is known of the functional role of individual TLRs in antifungal defenses. We found here that TLR7 was partially required for the induction of IL-12 (IL-12p70) by Candida albicans or Saccharomyces cerevisiae. Moreover, the IL-12p70 response was completely abrogated in cells from 3d mice, which are unable to mob-ilize TLRs to endosomal compartments, as well as in cells from mice

lacking either the TLR adaptor MyD88 or the IRF1 transcription factor. Notably, purified fungal RNA recapitulated IL-12p70 induction by whole yeast. Although RNA could also induce moderate TLR7-dependent IL-23 and tumor necrosis factor-alpha (TNF-α) secretion, TLR7 and other endosomal GSK1120212 TLRs were redundant for IL-23 or TNF-α induction by whole fungi. Importantly, mice lacking TLR7 or IRF1 were hypersusceptible to systemic C. albicans infection. Our data suggest

that IRF1 is downstream of a novel, nonredundant fungal recognition pathway that has RNA as a major target and requires phagosomal Selleckchem Selinexor recruitment of intracellular TLRs. This pathway differs from those involved in IL-23 or TNF-α responses, which we show here to be independent from translocation of intracellular TLRs, phagocytosis, or phagosomal acidification. Fungal infections, such as those caused by Candida, Aspergillus, and Cryptococcus spp., are a major public health concern, with Candida albicans representing the most frequent pathogenic species. This yeast often asymptomatically colonizes human mucosal surfaces and is found predominantly in the oral cavity, the gastrointestinal tract, and the vagina [1]. During commensal carriage, there is a tenuous balance between the body’s own defense systems and the remarkable ability of the organism to replicate in vivo. This equilibrium is frequently disrupted Protein kinase N1 by environmental factors that promote fungal growth or weaken host

defenses, leading to localized or systemic diseases [2]. Since the host immune status is the major factor that determines the transition of C. albicans from commensalism to pathogenicity, a better understanding of the mechanisms underlying recognition of and responses to fungi is the key to developing alternative strategies to control these infections. Anti-fungal defenses are initiated by the activation of germ-line encoded receptors (pathogen recognition receptors (PRRs)) after recognition of a relatively small number of highly conserved microbial components (pathogen-associated molecular patterns (PAMPs)). By this mechanism, each PRR links the recognition of a specific PAMP with the selective activation of a defined set of transcription factors [3].