Finally, to associate the appearance of the MHC class I dimers de

Finally, to associate the appearance of the MHC class I dimers described herein with alterations in the redox potential of cells undergoing hydrogen peroxide, Saracatinib nmr thimerosal and anti-CD95 treatments,

we directly measured redox activities using two methods. First we used the water-soluble tetrazolium salt (WST-8) to determine general dehydrogenase activity in the cells, and second we used monochlorobimane, which gives a direct fluorescent readout of intracellular GSH content.22 With both assay systems treatment of cells with hydrogen peroxide and thimerosal resulted in a profound reduction in signal (Fig. 4c,d). Treatment with anti-CD95 resulted in less significant loss of signal, which is a broad agreement with the immunoblotting results of Figs 2–4, where anti-CD95 induces fewer MHC class I dimers. In our previous work, we established that fully folded (i.e. recognized by conformation-specific monoclonal antibodies) MHC class I dimers exist on secretory exosome vesicles, and that these form by disulphide linkage between available cysteine residues in the cytoplasmic tail of many HLA-A and HLA-B molecules.15 In this study we extend

these observations and show that similar MHC class I dimers can be detected on cells in which the redox environment has been significantly altered, either by chemical oxidation with diamide, or chemically induced apoptosis with hydrogen peroxide and thimerosal, or by cross-linking of FasR/CD95. Control of dimer formation was likewise localized to the cytoplasmic tail domain cysteine located at residue 325, found in many HLA-B alleles. This is somewhat in contrast to previous observations wherein HLA-B27 dimer structures Tanespimycin nmr were observed even after removal of the cysteine at position 325,10,23 but this

may potentially be accounted for by the use of different cell lines and overall expression levels of the HLA-B27 heavy chain in different systems. For example, it is notable that in our CEM transfectants there was very little HLA-B27 dimer present in cell lysates in the absence of oxidative stress, as shown in Fig. 2, whereas the Jesthom cell line, which expresses higher levels of cell surface HLA-B27 than the CEM lines, displays dimers under MycoClean Mycoplasma Removal Kit normal conditions. Similarly, we have previously noted that HLA-B27 dimers tend to form in dendritic cells only after activation and significant up-regulation of MHC class I expression.24 Therefore, MHC class I expression levels and the redox status of cells may both contribute to dimer formation. In this current study we also generated a mutant form of HLA-B27 called S42C that mimics the dimer formed by the non-classical HLA-G molecule. None of the treatments applied in this current report significantly increased the dimer population over that already formed in the absence of treatment (Fig. 2a and data not shown), and indeed even the strong oxidant diamide failed to induce the formation of a 100% dimer population in all our studies.

2% in Australia A low awareness rate in contrast to high prevale

2% in Australia. A low awareness rate in contrast to high prevalence of CKD is Apoptosis Compound Library in vitro a serious public health problem in Taiwan. Hsu et al. 8 reported an overall awareness rate of CKD of 9.7% in contrast to 6.9% prevalence rate for CKD stage 3–5. Awareness rates for each stage of CKD were 8.0% (stage 3), 25.0% (stage 4) and 71.4% (stage 5). In Wen’s report,13 the overall awareness of CKD stage 1–5 was only 3.5%. Awareness rates for each stage of CKD are 2.66% (stage 1), 2.68% (stage 2), 4.10%

(stage 3), 23.67% (stage 4) and 52.40% (stage 5). Notably, low awareness in contrast to high prevalence of CKD is especially more common in subjects of low socioeconomic and educational status. This fact raises the importance of promoting awareness of CKD through patient education and an intensive screening program. For example, World Kidney Day and a public media campaign have been implemented in Taiwan since 2007. More importantly, continuing medical education is crucially needed for each level of medical physician in all specialties. We must foster the health-care professionals to learn the new concept of CKD definition buy SB431542 and classification4 and to provide the rational care for this rapidly growing population of CKD. Taiwan has the highest incidence and prevalence rate of ESRD based on international comparisons of the USRDS report.11 Based on the

National Dialysis Registry by the Taiwan Society of Nephrology (TSN), Yang et al. reported that from 1990 to 2001 incidence and prevalence rates of ESRD patients increased 2.6 times from 126 to 331/million populations (pmp) and 3.46 times from 382 to 1322/pmp, respectively, from 1990 to 2001.27 Recent data from the Dialysis Registration of the TSN in 2007 reported 48 072 haemodialysis

(HD) and 4465 peritoneal cases, corresponding to a prevalence of 2288/pmp and incidence of 415/pmp, respectively.11 The heavy burden of renal replacement therapy by dialysis was managed by a total of 1081 board-certificated nephrologists, 534 dialysis centres and 14 502 HD machines. Moreover, the domestic renal transplant patients from 1997–2007 were 2054 cases based on the data of the Bureau of National Health Insurance (BNHI). However, it was estimated that another 50% of patients received this website off-shore renal transplantation, mainly from China. There are several possible explanations for the high incidence and prevalence of ESRD in Taiwan. First, a major reason is that the launching of the NHI in 1995 provided free coverage for dialysis therapy without co-payment.28 The universal coverage facilitates the utilizations of renal replacement therapy and further accelerates the inflow of dialysis patients. Second, the better health-care system may improve the survival rate of chronic diseases patients and increase the overall life expectancy. This reason is supported by the evidence that the increased ESRD population consisted of mainly elderly (>65 years) and diabetic patients in Taiwan.

9 Our results, showing severely impaired function of the D501N m

9. Our results, showing severely impaired function of the D501N mutant, are consistent with the earlier report 9. However, our results obtained for the R299W mutant are inconsistent with Kavanagh et al.9, who reported impaired function of R299W towards degradation of both C4b and C3b. Here, we observe diminished secretion but normal function.

Perhaps these discrepancies can be explained in terms of different purification techniques or how the functional analyses were performed. Mutations were investigated at a structural level using previously reported homology models of each independent FI domain. A structural investigation of the full-length FI model is not possible at present because there are not Pexidartinib yet enough experimental data to position the domains in relation to one another. However, for several mutations, M120V, H165R, A222G, D501N, the structural analysis is fully consistent with the observed experimental data, thereby allowing rationalization with the possible pathological nature of the substitution or the lack thereof (Table 2). This investigation suggests also that the area around His165 could be solvent exposed in the full-length protein. As we do not have a 3D model structure for the region of residue 299, we could not analyze the replacement

of the polar and most likely positively charged Arg299 by a bulky aromatic Trp. However, the lack of conservation of this residue in the sequences of various species suggests that it could be replaced Alisertib supplier without creating major folding/stability problems, as indeed noted experimentally. Additional work

will be required to understand in detail the P32A and N133S substitutions since these residues could be at the domains’ interfaces or involved in protein–protein interactions. The mutations identified in aHUS patients are heterozygous, in contrast to FI-deficient patients, who have homozygous or compound heterozygous mutations 34. The main difference between these two patient groups is the consumption of C3; FI-deficient patients have very low levels of C3 whereas levels in aHUS patients are normal or only moderately reduced. It is the C3 in aHUS patients that enhances kidney damage. FI-deficient patients CHIR-99021 price can also have kidney problems such as glomerulonephritis, but this differs from the microangiopathies in the kidneys of aHUS patients. We found that in most patients the level of FI in plasma was decreased when the corresponding mutant (C25F, W127x, N133S, L289x, R456x, T520x and W528x) was showing impaired secretion from HEK 293 cells. However, there were a few exceptions from this rule (M120V, A222G, R299W and W468x) where there was no decrease of FI plasma level despite the fact that secretion of these mutants was impaired. Most likely, this discrepancy can be explained by the fact the FI levels in normal healthy people and patients with mutations in CFI vary a lot since FI is an acute-phase protein.

Networks are displayed graphically as gene/genes products (nodes)

Networks are displayed graphically as gene/genes products (nodes) and the biological relationships between the nodes (edges). All edges are supported by at least one reference from

the literature, or from canonical information stored in the Ingenuity Pathways Knowledge Base. In addition, IPA computes a score for each network according to the fit of the user’s set of significant genes. The score, representing the – log(P-value), indicates the likelihood Dabrafenib of the Focus Genes in a network from Ingenuity Knowledge Database being found together randomly. We identified X chromosome sites that were consistently hypermethylated (n = 18, Table 1) and hypomethylated (n = 25, Table 2) in affected twins. Within the 5-kb window sampled for each X-linked gene, most of the differentially methylated regions (DMRs) were located in promoter regions or CpG islands while two hypermethylated (48980151–48980208 and 104355356–104355413) and six hypomethylated (103883076–103883125, high throughput screening 47226194–47226247, 134532227–134532289, 134532327–134532376, 134532427–134532476, 134532627–134532676) DMRs were found downstream

of the transcription start sites. In all cases, DMRs were associated with known genes and we noticed that IL1RAPL2 was found in both lists (the two hypermethylated sites are downstream of the hypomethylated one). In some cases, multiple DMRs belong to the same gene (as in the case of hypomethylated peaks acetylcholine 134532227–134532289, 134532327–134532376, 134532427–134532476 and 134532627–134532676 onto gene DDX26B) or a specific site is located in a CpG island of

a bidirectional promoter for two different genes (i.e. hypomethylated peak 152712287–152712338 for genes SSR4 and IDH3G). Three hypomethylated peaks are associated with intergenic single-nucleotide polymorphisms (SNP), with peak 13087308–13087357, including SNP rs61677044, peak 13087708–13087757 falling in a region 150 bp downstream from SNP rs16978681, peaks 126140539–126140588 and 126140739–126140788 mapping to a SNP-rich region. Genes identified by the hypermethylated and hypomethylated sites encode for proteins that are illustrated in Tables 3 and 4, respectively. The 26 proteins include transcription factors, membrane and soluble enzymes, surface antigens and translocation proteins while in some cases proteins are currently defined only structurally, but not functionally. We explored possible functional relationships between the 26 genes using the IPA Knowledge Database. Unsupervised IPA network analysis identified a single cluster of 25 genes that included seven of our 26 genes and 18 additional genes, which was unlikely to occur by chance (P = 10−13). The plausible biological network generated is shown in Fig.

g CVDs, less manageable diabetes) associated with this and other

g. CVDs, less manageable diabetes) associated with this and other local diseases. Chronic periodontitis (CP) is one of (if not) the most common chronic inflammatory diseases known to mankind. It is not only the most common cause of tooth loss in adults but has also been associated, in a number of studies, with an increased risk for various Olaparib concentration medical disorders including cardiovascular disease

(CVD) (Genco & Stamm, 1998; Kuula et al., 2009), reduced diabetic control (Mealey & Ocampo, 2007), preterm delivery (Radnai et al., 2009) and osteoporosis (Golub et al., 2008). Destructive CP is initiated by infection with specific bacterial species, particularly anaerobic gram-negative microorganisms such as Porphyromonas gingivalis, but the breakdown and loss of the periodontal connective tissues, including bone, are primarily the result of the host response, particularly the production of inflammatory mediators (prostanoids, cytokines, nitric oxide), and neutral proteinases, particularly the matrix metalloproteinases (MMPs; e.g. collagenases and gelatinases) and serine proteinases (e.g. elastases) (Ryan, 2002; Lamster et al., 2008; Persson & Persson, 2008).

Chronic inflammatory conditions including CP are characterized by a local accumulation of leukocytes, predominantly (70%) mononuclear cells. Endotoxin derived from P. gingivalis, a virulent periodontal pathogen, can induce the production of proinflammatory cytokines in monocytes. These mediators exert autocrine and/or paracrine Apitolisib clinical trial activities by upregulating the expression of various proteinases including MMPs, resulting in the destruction of connective tissue including periodontal tissues. Because recent studies have also linked this oral infection with an increased risk for developing for a number of systemic disorders including CVD (Genco & Stamm, 1998; Kuula et al., 2009), it is essential to optimally

control this oral disease and maintain periodontal health. In our lab, we have repeatedly shown that tetracycline derivatives, some with no antimicrobial activity, can reduce inflammatory tissue damage (Ryan et al., 1996). We have previously shown that the activities of the polymorphonuclear leukocyte MMPs, MMP-8 and MMP-9, can be inhibited by therapeutically relevant doses of chemically modified nonantibiotic tetracyclines (Golub et al., 1995). In the current study, we used a complete interstitial extracellular matrix (ECM) secreted by R22 smooth muscle cells as a model system (Gu et al., 2005) to determine whether doxycycline (a tetracycline antibiotic) can inhibit inflammatory cytokines and MMPs in mononuclear cells, thereby preventing connective tissue breakdown. All chemical reagents, lipopolysaccharide and doxycyline were purchased from Sigma-Aldrich Co. (St. Louis, MO).

e expressing at least one of the markers) This clearly confirme

e. expressing at least one of the markers). This clearly confirmed that degranulation became increasingly dominant after transplantation, with a median of 92% of CD8+ pp65-specific T cells and 85% of IE-specific CD8+ T cells expressing this marker (alone or in combination) after transplantation compared with 84% and 71%, respectively, in controls (not shown). However, because of their likely protective role, we were primarily interested in the effect of immunosuppression on the T cells producing IFN-γ, TNF-α and IL-2 simultaneously, or any two

of them.9 For this purpose, the analyses shown in Fig. 1(b) disregard degranulation and focus on IFN-γ, TNF-α and IL-2 alone. They show that

the most dominant CMV-specific CD8+ subset Kinase Inhibitor Library order (as defined by these functions) in healthy donors produces just IFN-γ and TNF-α, while the subset producing all three measured cytokines is the only other sizeable subset. Both are strongly reduced in transplant patients. A similar distribution was observed for pp65-specific CD8− T cells. When studying each of 15 non-overlapping functional subsets individually (Boolean gating) it became apparent that T cells exhibiting degranulation as a single function were dramatically increased in transplant patients (Fig. 1c). As all patients received calcineurin inhibitors (but only one-third each received everolimus or mycophenolate mofetil), we attempted to reproduce this effect in vitro by incubating donor-derived cells overnight with the KPT-330 in vivo calcineurin inhibitors cyclosporin A or tacrolimus before stimulation, because these were the most likely

drugs to cause this change. This resulted in a dose-dependent reduction of polyfunctionality; the subsets producing IFN-γ, TNF-α and IL-2, or IFN-γ and TNF-α decreased (Fig. 2a,b) whereas subsets displaying only single functions emerged and increased (Fig. 2c,d). Dot plots in Fig. 2(e) show a dose-dependent decrease in TNF-α, IFN-γ and IL-2 production, but little effect on degranulation. Our results show that immunosuppression induces marked changes in the CMV-specific T-cell response after heart and lung transplantation. These are reflected in response quality (i.e. the functional response profile) Farnesyltransferase rather than quantity (i.e. the number of inducible cells). The most obvious effects were reduction of IL-2 and TNF-α production, IFN-γ seemed somewhat less affected and degranulation not at all. This predominantly translated into the generation of T-cell subsets with one single function, most frequently degranulation, at the expense of subsets displaying IFN-γ, TNF-α and IL-2 at the same time. Degranulation was the most inclusive marker of total response size but not the most informative with regard to the effect of immunosuppression.

38 We then

determined if the phenotypic and endocytic dif

38 We then

determined if the phenotypic and endocytic differences between MoDCs and BDCs translated into differences in their ability to induce T-cell proliferation using autologous T cells. To this end, pigs were vaccinated with PTd and isolated cells were re-stimulated in vitro with two different antigens to be able to compare naive versus primed T cells. When the antigen OVA was used to address stimulation of naive T cells, BDCs induced Staurosporine cost less proliferation compared with MoDCs. However, when PTd was used for stimulation of autologous primed T cells, the extent of proliferation was the same between MoDCs and BDCs. As the activation threshold for naive T cells is higher because of an uncoupled signalling machinery,39,40 we assume that T cells to which OVA was presented were naive and required more signals that the BDCs were less able to provide. This could be attributed to their

lower endocytic ability. With respect to primed T cells, however, BDCs did not differ from MoDCs in their ability to drive T-cell proliferation, which may be a result of a lesser need for additional stimulation. It has also been demonstrated that the pDC population within the BDCs is better able to induce proliferation in antigen-experienced T cells compared with naive T cells.41 Therefore, porcine BDCs differ from MoDCs in their ability to stimulate Roxadustat ic50 naive T-cell proliferation but not primed T-cell proliferation. This is in contrast to observations made in mice41 and provides further evidence that BDCs indeed are able to drive T-cell activation in both naive and memory T cells.39 In summary, in the present study we compared two populations

of DCs in their phenotype, endocytic ability, response to LPS stimulation and ability to induce an antigen-specific immune response in pigs. The findings suggest that BDCs, which contain both pDCs and cDCs, are less endocytically active than MoDCs and have a lower expression Sclareol of CD80/86. They also have lower basal cytokine protein concentrations but in response to stimulation with LPS, there is a higher fold increase in response despite the absolute amounts being lower in MoDCs. Furthermore, this is the first time in the pig that chemokines have been examined in response to LPS in both MoDCs and BDCs and it allows for a more comprehensive view of DC behaviour. Lastly, both MoDCs and BDCs are able to induce T-cell proliferation, which is in contrast to observations made in mice,41 and which will further the understanding of these important cells and their role in driving antigen-specific immune responses. We are grateful to all members of the Animal Care Unit at VIDO for their help in isolating large amounts of blood and for housing the pigs. We are especially thankful to Amanda Giesbrecht and Jan Erickson. We also thank Krupal Patel, Stacy Strom and Justin Gawaziuk for their help in isolating PBMCs and DCs.

Modifiable risk factors such as obesity, lifestyle, sleep positio

Modifiable risk factors such as obesity, lifestyle, sleep position and medication usage should be addressed. Proteinuria has been described in SA.54–57 Urine dipsticks have shown greater degrees of proteinuria when performed at the time of polysomnography.54,55 Quantification of urine protein has also demonstrated greater proteinuria in SA patients compared with those without SA.56 Case reports have described

improvement or even resolution of proteinuria with treatment of SA.57 Not all studies have shown the association of proteinuria with SA however.58 The potential causes of proteinuria in SA are similar to factors associated with SA and CKD. Focal segmental glomerulosclerosis as discussed above is one plausible lesion that may occur with SA and result in proteinuria. The heightened sympathetic tone and intermittent intrarenal Proteasome inhibitor haemodynamic changes caused by apnoea and hypopnoea may potentially lead to damage within the nephron. Ischaemia and reperfusion injury can lead to oxidative stress and free radical formation as previously described.52,59 Lower circulating nitric oxide levels have been demonstrated in SA patients compared with the general population, further suggesting hypoperfusion and ischaemia.60 Elevated vascular endothelial growth

factor levels have been demonstrated in SA patients.61 Repetitive injury to the kidney as described above can lead to transient and even sustained damage within the kidney. In the obese patient EPZ-6438 mouse with isolated proteinuria, screening for SA may be warranted as part of the work-up. Isolated proteinuria is detrimental to renal function. Moreover, this subset of patients is at greater risk for complications of SA such as heart disease and cerebrovascular disease.

Aggressive treatment of SA with positive airway devices or lifestyle medication should be important in this population. The relationship between renal transplant and SA can be viewed as a paradox. As mentioned above, renal transplant can potentially improve SA in the dialysis population but the post-transplant state adds another dimension of risk for SA specifically by predisposing patients to the metabolic syndrome. Case reports have shown renal transplantation improves or cures SA in patients on dialysis.31,39,40 If the uremic milieu were responsible for SA, the cure Y-27632 2HCl of SA by renal transplantation seems plausible in a subset of patients who develops SA during dialysis. However, the few cases of cure after renal transplantation have not translated into an overall lower rate of SA in renal transplant patients compared with dialysis patients. The actual prevalence of SA in renal transplant patients may be comparable with the dialysis population. Although the Berlin Sleep Apnea Questionnaire has not been validated in CKD patients, Molner et al.62 used the Berlin Sleep Apnea Questionnaire to assess risk of SA in 1037 kidney transplant patients and 175 patients wait-listed for transplant.

In the intervention setting, follow-up studies of alum-conjugated

In the intervention setting, follow-up studies of alum-conjugated glutamic acid decarboxylase immunization (GAD-Alum), after initial successful pilot data [29], have been disappointing at Phase II [30] and Phase III stages [12]; a secondary prevention Doramapimod purchase study is in progress (Table 1). New modalities of ASI have emerged, however, including peptide and DNA-based deliveries, in some cases associated with positive biomarker data [16, 31] and in the case of Diapep277, with

evidence of clinical effectiveness (see discussion above and Table 3). Full reporting of the proinsulin-DNA vaccine and Diapep277 Phase III studies are eagerly awaited. In terms of development, however, it is notable that, for example, in the intervention setting, there has been no attempt as yet to combine antigen with any other treatment modality (Fig. 2), despite encouraging preclinical

data [32, 33]. With the somewhat high number of failed clinical trials in type 1 diabetes in the past few years, it has become increasingly tempting to attribute some of the blame to animal models. One often hears remarks such as ‘animal models have misled us’ and the near-ubiquitous comment ‘mice are not humans’. Clearly, we are all aware that diabetes in various rodent models may only model in part how type 1 diabetes develops in humans. However, we would like to argue here that animal models have a key place in the clinical translation for therapeutic approaches in autoimmune disease overall, as long as they are used correctly, not selleck products over-interpreted

and analysed carefully. It should be helpful, therefore, to first take a closer look at the extent to which animal studies diverge from human trials. Several ASI trials in man have reported negative (or positive substudy) results (GAD-Alum, Montelukast Sodium oral insulin and intravenous insulin); have shown marginal effects (BayHill DNA vaccine, Diapep277); or were not powered to demonstrate efficacy, yet have not shown any strong clinical effects in established diabetes (adjuvanted insulin B-chain peptide, proinsulin peptide). Each trial is distinctly different and it is therefore worthwhile to look at the facts one by one. Subcutaneous administration of GAD-Alum was developed on the basis of earlier studies by several teams, which had all used GAD peptides to prevent diabetes in the non-obese diabetic (NOD) mouse spontaneous disease model [34, 35]. Others have since prevented type 1 diabetes successfully with oral GAD and in some cases GAD DNA vaccines also using other diabetes models [36]. A crucial difference between the human trial and all the preclinical studies is that immunization with GAD always worked to prevent diabetes, yet never after diabetes onset.

They found, by

using HEK293 cells transfected with both T

They found, by

using HEK293 cells transfected with both TLR2 and CD14, that TLR2 is recruited within lipid rafts following LTA stimulation, that LTA is internalized in a lipid-raft-dependent manner and that TLR2 is co-localized with LTA in the Golgi apparatus.15 However, they concluded that LTA internalization is not dependent on TLR2, because LTA internalization occurs even in HEK293 cells transfected with only CD14.15 This is in good agreement with our finding that FSL-1 is internalized into PMφs from TLR2−/− mice (Fig. 7c,e). However, their findings that LTA Proteases inhibitor is internalized into a cell in a lipid-raft-dependent manner and is co-localized with TLR2 in the cytosol15 are in contrast to our findings that FSL-1 is internalized in a clathrin-dependent manner (Figs. 3,4) and FSL-1 is not co-localized with TLR2 in the cytosol (Fig. 7a). This discrepancy may be because of the difference in cell types and ligands used. Triantafilou et al. used non-phagocytic HEK293 transfectants with LTA, whereas we used professional phagocytes, RAW264.7 cells. In addition, several

lines of evidence have indicated that LTA is not a TLR2 ligand.34–36 They have described that contaminants in the LTA preparation, but not LTA itself, are responsible PF-562271 for TLR2-mediated activation of innate immune cells. For these reasons there can be no doubt about the difference in uptake mechanisms between LTA and FSL-1. More recently, Triantafilou et al.37 have also reported that TLR2 is co-localized with TLR6 and CD36 in the Golgi apparatus after stimulation with FSL-1 in HEK293 cells transfected with CD14, TLR2, TLR1, TLR6 and CD36, although they did not investigate whether FSL-1 is co-localized with TLR2 in the cytosol.37 Taken together, these results suggest that TLR2 ligands are internalized into cells irrespective

of the presence of TLR2 after recognition by TLR2. There was great interest as to what kind of receptors other than TLR2 are involved in the FSL-1 uptake. We speculated that CD14 or CD36 may mediate the Atorvastatin uptake, because they function as co-receptors of TLR2 to recognize lipopeptide.32,33 CD36 is a glycosylated transmembrane protein that is expressed in various cell types and tissues including monocytes/macrophages.38 Especially for innate immune responses, Hoebe et al.32 showed that CD36 is involved in the recognition of TLR2/6 ligands. CD36 is also known as a class B scavenger receptor, and it has been reported that the C-terminal cytoplasmic domain of CD36 is required for bacterial internalization.39 Therefore, it is reasonable that CD36 is responsible for FSL-1 uptake, although Mairhofer et al.40 showed that most of the CD36 is in the lipid-raft fraction. CD14 is found in a soluble form in serum or as a glycosylphosphatidylinositol-anchored protein on the cell membrane, and is one of the essential accessory proteins for lipopolysaccharide recognition.41 It is also known that CD14 functions as a co-receptor of TLR2 for the recognition of a triacylated lipopeptide.