Moreover, the presence of more than one locus homologous to disruption constructs may also lead to additional ectopic integration, which may explain the occurrence of additional ectopic bands in five TmSSU1Δ mutants (data not shown). In conclusion, it is advantageous to use TMLIG4-defective cells in gene targeting experiments.

Further experiments to elucidate the NHEJ pathway in T. mentagrophytes are required. This research was partially supported by a Grant-In-Aid (19590457) from the ministry of Education, Science, Sports and Culture of Japan (KM). Table S1: Primers used in this study. “
“The scaffold protein caspase recruitment domain-containing protein 11 (CARD11) is implicated in the regulation of inflammation and autoimmunity. The present study aimed to explore the role of CARD11 in the pathogenesis of rheumatoid arthritis (RA). Mice with collagen-induced arthritis see more (CIA) were treated with either CARD11-targeted interfering RNA (CARD11

siRNA) or control siRNA by intraperitoneal injection Selumetinib chemical structure every 3 days after CIA establishment. The clinical score of arthritis was recorded every other day. Synovial inflammation and cartilage erosion were evaluated by histology and microcomputed tomography (micro-CT). Serum anti-type II collagen (anti-CII) antibodies and cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The CARD11/Bcl10 formation Enzalutamide cost and nuclear factor-kappa B (NF-κB) activation was assessed by immunoprecipitation and immunoblotting, and the percentage of T helper type 17 (Th17) cells was determined by flow cytometry. Systemic administration of CARD11 siRNA significantly reduced the clinical score of CIA severity. As indicated by the histology,

joint inflammation and destruction were attenuated by CARD11 siRNA treatment. Micro-CT demonstrated less severe joint destruction in CARD11 siRNA-treated mice than in control mice. CARD11 siRNA treatment resulted in inhibition of CARD11/Bcl10 formation and the subsequent NF-κB activation. In addition, treatment with CARD11 siRNA resulted in a pronounced decrease in proinflammatory cytokines interleukin (IL)-1β, IL-6 and IL-17. Serum anti-CII antibody and the percentage of Th17 cells were also significantly reduced. CARD11 is involved in the pathogenesis of CIA by formation of the CARD11/Bcl10 complex and enhancement of the Th17 cell response. Targeting CARD11 provides a novel research direction in the development of therapeutic strategies for RA. “
“To investigate the usefulness of serum cytokine levels in the diagnosis of active cystic echinococcosis, we evaluated the cytokine profile of patients with hepatic cystic echinococcosis in different cyst stages, CE 1-2 (active), CE3a-3b (transitional) and CE4-5 (inactive). Ex vivo assessment of Th1 (IL12, TNFα) and Th2 (IL4, IL10) cytokines in sera was carried out using ELISA.

This point notwithstanding, IFN-β is released following STING activation by cytosolic DNA sensors such as cGAS, and IFN-β is a potent activator of innate (e.g. APCs) and adaptive (T/B cells) immune cells. However, activated immune cells may drive dominant immunogenic or tolerogenic responses, contingent on other factors in affected microenvironments that shape downstream responses to (i) insults driving immune responses and (ii) other ISGs responsive to IFN-β [21]. To illustrate this paradigm with a specific example, oligonucleotides containing unmethylated CpG dimers (CpGs) ligate TLR9 and are

widely regarded as immune stimulator adjuvants. However, when CpGs were administered systemically (by intravenous injection) to mice, antigen-specific Th1 or Th2 effector responses elicited in vivo were suppressed in spleens or lungs in a CpG dose-dependent Alectinib mw manner [22-26]. Consistent with the widely known immune adjuvant properties of TLR ligands, low CpG doses (25 μg) enhanced splenic Th1 responses. In striking contrast, higher

CpG doses (100 μg) suppressed splenic Th1 responses due to IFN-αβ-mediated IDO induction in a subset of DCs expressing the Y27632 B-cell marker CD19, which activated Treg cells [22-24]. Thus, IFN-αβ signaling is the pivotal driver of both stimulatory (Th1) and Treg responses to TLR9 ligands, and IDO is the critical ISG driving dose-dependent immune regulatory outcomes Montelukast Sodium following TLR9 ligation in vivo. As TLR9-sensing induces IFN-αβ release at high and low doses, it is unclear why IDO induction was dose-dependent, although one potential explanation is that there are lower local IFN-αβ signaling thresholds for inducing immunogenic responses than IFN-αβ signaling thresholds for inducing CD19+ DCs to express IDO. IDO is not the only ISG that regulates

immunity and IFN-αβ signaling may synergize with regulatory cytokines (e.g. TGF-β, IL-10) to drive dominant regulatory outcomes in some inflammatory settings. For example, systemic exposure to apoptotic cells, which drives tolerogenic responses, was shown to stimulate the release of regulatory (TGF-β, IL-10) and proinflammatory (IL-6, TNF-α, IL-12) cytokines in spleens of mice [27]. However, administering IDO inhibitor at the same time enhanced proinflammatory but reduced regulatory cytokine production and drove effector T-cell responses [27], indicating that the balance of proinflammatory and regulatory cytokines, and not the release of specific cytokines per se, is the critical factor influencing immune outcomes. The key lesson from these studies is that cytosolic DNA sensing to activate STING and drive IFN-β release may have tolerogenic or immunogenic consequences in physiologic settings of inflammation that are relevant to clinical disease, including autoimmune syndromes, cancer, and chronic infections.

28 These findings prompted us to investigate the effects of B7-H3-transduced tumour cells on anti-tumour immunity, because XL765 CD8+ T cells are the major effector cells in most cases of tumour eradication. In this study, we examined mechanisms of enhanced anti-tumour immunity induced by tumour-associated B7H3 and the involvement of its TLT-2 receptor. Female C3H/HeN, DBA/2, BALB/c, C57BL/6 (B6) and BALB/c nude mice were purchased from Japan SLC (Hamamatsu, Japan), Charles River Japan (Tokyo, Japan) and CLEA Japan (Tokyo, Japan). Chicken ovalbumin (OVA)257–264-specific TCR transgenic OT-I mice

were generously provided by Dr William R. Heath (The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia).30 Mice were 6–10 weeks of age at the start of the experiments. All experiments were approved by the Animal Care and Use Committee of Tokyo Medical and Dental University. The T lymphoma EL4, OVA-expressing

EL4 (E.G7), plasmacytoma J558L, mastocytoma P815 and melanoma B16 cell lines were cultured in RPMI-1640, supplemented with 10% fetal bovine serum and 10 μg/ml gentamicin. A squamous cell carcinoma SCCVII cell line was maintained ATM/ATR assay in Dulbecco’s modified Eagle’s medium with 10% fetal bovine serum and 10 μg/ml gentamicin. Anti-B7-H3 [MIH32 and MIH35, both rat immunoglobulin G2a (IgG2a), κ] and anti-TLT-2 mAb (MIH47, rat IgG2a, κ and MIH49, rat IgM, κ) were generated as described previously.28 These mAbs were biotinylated or conjugated with fluorescein isothiocyanate (FITC), according to a standard protocol. Peridinin-chlorophyll-protein complex-carbocyanin 5.5 (PerCP-Cy5.5) -conjugated-anti-CD4 (GK1.5), anti-CD8 (53-6.72), and anti-CD3 (145-2C11); FITC-conjugated anti-CD45 (3F11.1); anti-major histocompatibility complex (MHC) class I (SF1-1.1, 36-7-5 and AF6-88.5 for Kd, Kk and Kb, respectively); phycoerythrin-conjugated Erythromycin anti-CD8 (53-6.72),

anti-CD25 (PC61), anti-CD69 (H1.2F3), anti-CD54 (YN1/1.7.4), anti-CD80 (1G10) and anti-CD86 (GL1) mAbs; and appropriate fluorochrome-conjugated isotype control immunoglobulins were used. All fluorochrome-conjugated antibodies except FITC were obtained from eBioscience (San Diego, CA) or BD-Pharmingen (San Diego, CA). Culture supernatant from the 2.4G2 hybridoma (anti-CD16/CD32 mAb) was used to block Fc-mediated binding. Phycoerythrin-streptavidin or allophycocyanin-streptavidin was used for the biotinylated mAbs. Cells were stained and analysed using a fluorescence-acitvated cell sorter (FACSCalibur; BD Biosciences, Sparks, MD) and the CellQuest (BD Biosciences) or flowJo (TreeStar, Ashland, OR) software. Mouse B7-H3 complementary DNA28 was inserted into the pMKITneo, pMXC and pMXs-neo (kindly provided by T. Kitamura) expression vectors.

Interestingly, drugs that interfere with NF-κB activation significantly antagonise the immunoregulatory effect of MSCs, which could have important implications for find more immunosuppression regimens in the clinic. “
“Mature naive CD4 T-cells possess the potential for an array of highly specialized functions, from inflammatory to potently suppressive. This potential is encoded in regulatory DNA elements and is fulfilled through modification of chromatin and selective

activation by the collaborative function of diverse transcription factors in response to environmental cues. The mechanisms and strategies employed by transcription factors for the programming of CD4 T-cell subsets will be discussed. In particular, the focus will be on co-operative activity of environmental response factors in the initial activation of regulatory

DNA elements and chromatin alteration, and the subsequent role of ‘master regulator’ transcription factors in defining the fidelity and environmental responsiveness of different CD4 T-cell subsets. Mature naive CD4 T-cells, when poised for effector differentiation, are near their final destination following a long developmental journey. Mesoderm-derived haemangioblasts – the RG7204 multipotent progenitors of both endothelial cells and haematopoietic cells – develop into the embryonic haemogenic endothelial cells of the dorsal aorta. Definitive haematopoietic stem cells derived from this diminutive see more tissue go on to seed the fetal liver and eventually

the adult bone marrow. These self-renewing haematopoietic stem cells differentiate into the common myeloid and common lymphoid progenitor cells that form the basis for the plethora of devoted immune cell lineages, including CD4 T-cells. Along this broad spectrum of differentiation – from germ layers to T-cell subsets – a number of mechanistic strategies are employed to access new developmental potential while restricting alternative fates. Conrad Waddington (1905–1975) considerably progressed thinking on cellular differentiation by proposing that genes (and mutations) can affect differentiation potential. He visualized this concept as a marble rolling through an ‘epigenetic landscape’, shaped by the action of genes, with ridges and valleys representing irreversible developmental commitment and future potential (Fig. 2, reviewed in ref. [1]). Spatial and temporal control of gene expression creates this ‘epigenetic landscape’ and instructs diverse cellular differentiation from a single common genome. Mechanisms controlling varied gene expression can include instructive morphogen gradients, asymmetric cell division, and natural distributions or stochastic action of signalling, nuclear, or chromatin-associated factors (gene expression noise[2]) together with feedback and ‘feedforward’ transcriptional networks.

Methods: Audit of medical records for (1) 58 patients who received ACP (2010–2012) and (2) 58 age and gender matched control patients (2007–2009). Results: The rate of withdrawal from dialysis was significantly higher in the implementation Torin 1 solubility dmso group (IG) (P = 0.022), as was the involvement

of the patient or family in the decision to withdraw dialysis (P = 0.001). Medical decisions to withdraw dialysis was equal between groups (P > 0.05) More ACP documents were completed in the IG (MEPOA = 67%, SOC = 27%, RTC = 17%) compared to the control group (MEPOA = 5%, SOC = 10%, RTC = 2%). Significantly more wishes were correctly documented in the IG (P < 0.001) and more changes to patient management plans were observed (71%). Patients in the IG were more likely to have their wishes respected (P = 0.007) and receive treatment in their best interest (P < 0.001). Discussion: The implementation of ACP led to patient wishes being documented and respected, and to dialysis being withdrawn at learn more the patient’s or family’s request. No difference

observed in the involvement of the medical team. More wishes were respected in the IG and more patients received treatment that was in their best interest. Conclusion: Facilitated ACP successfully increased the likelihood of wishes being respected and patients receiving treatment in their best interest. 183 THE ROLE OF THE VASODILATOR R-A-A SYSTEM IN HYPERTENSIVE PREGNANCY F PETTIT1, J SPAAN1, GJ MANGOS1,2, G DAVIS3, A HENRY3, M BROWN1,2 1Department of Renal Medicine St George Hospital Sydney; 2Department of Medicine University of New South Wales; 3Department of Women’s and Children’s Health St George Hospital Sydney, Australia Aim: To examine the activity of the ACE2/Ang(1–7) axis of the RAAS in normal and hypertensive pregnancy. Background: A novel vasodilatory pathway of the RAAS has been described,

including the angiotensin converting enzyme 2 (ACE2) and the vasodilator Ang(1–7). The pressor effects of Angiotensin-II (Ang-II) are reduced in normal pregnancy, and partially restored in pre-eclampsia. This may be explained by alteration in the balance between the vasoconstrictor and vasodilator components of RAAS. Methods: Women in their 3rd trimester in a cross sectional study. There were five Tyrosine-protein kinase BLK groups: normotensive pregnancy (NP); gestational hypertension (GH); essential hypertension (EH), pre-eclampsia (PE) and non-pregnant controls (C). Each study participant had blood taken for biochemistry and haematology as well as Renin level, Aldosterone, ACE1&2, Angiotensin II and Ang(1–7). Results: 122 women have been recruited to date; NP = 20, GH = 49, EH = 15, PE = 11 and C = 27. Hormone results are available on 95 subjects. Renin levels were higher in NP-30 U/L compared to C-19 mU/L (P < 0.05). NP-30 U/L levels were significantly higher than in EH-19 mU/L and PE-17 mU/L (P < 0.05) but similar to GH-26 U/L.

SHIN HO SIK1, GWOO SANGEON1, KIM YE NA1, JUNG YEON SOON1, RIM HARK1, HYUN YUL RHEW2 1Department MLN0128 order of Internal Medicine, Kosin University College of Medicine; 2Department of Urology, Kosin University College of Medicine Introduction: Several registries and centers have reported the results of

renal biopsies from different parts of the world. As there are few data regarding the epidemiology of glomerulonephritis (GN) in South Korea, we conducted this study of renal biopsy findings during the last 20 years in our center. Methods: Data for 1054 patients who underwent renal biopsy at our center between 1992 and 2011 were collected retrospectively, including demographic data and renal syndrome at presentation. All kidney specimens were studied with light and immunofluorescent microscopy. Results: There were 926 cases of native kidney biopsies and 128 cases of allograft kidneys. Pathologic results were categorized according to the ages of patients at the time of renal biopsy: ≤15 years (children), 16–59 Ceritinib years (adults) and ≥60 years (elderly). In cases of primary GN, the most frequent type of renal pathology in children was mesangial proliferative

GN (MsPGN, 52.9%) followed by IgA nephropathy (IgAN, 23.5%) and minimal change disease (MCD, 11.8%). In adults, the most frequent type of renal pathology was MsPGN (34.5%) followed by IgA nephropathy (IgAN, 34.3%) and membranous proliferative GN (MPGN, 8.0%). In the elderly, the most frequent pathologic result was MsPGN (23.1%) followed by membranous GN (MGN, 17.9%), focal segmental global sclerosis Fenbendazole (FSGS, 12.8%) and crescentic GN (10.3%). In allograft biopsies, the most frequent type of renal pathology in adults was acute cellular rejection (35.4%) followed by chronic rejection (21.9%) and transplant glomerulopathy (9.4%). In native

kidney biopsies, the predominant presentation was asymptomatic urinary abnormalities (76.4%) followed by nephritic syndrome (17.1%) and acute kidney injury (AKI, 4.4%). Conclusion: Among 1,054 renal biopsy specimens, MsPGN and IgAN were the most frequent biopsy-proven renal diseases. MGN was the third most common cause of primary glomerular disease, and lupus nephritis was the most common secondary glomerular disease. Our data contribute to the epidemiology of renal disease in South Korea. MORIKAWA TAKASHI1,2, YAMAZAKI DAISUKE1, DAGA HARUKO2, NISHII YUKA1, SHIBATA MIKIKO1, OHNO YOSHITERU1, HAMADA MASAHIRO1, KISHIDA MASATSUGU1, KITABAYASHI CHIZUKO1, KONISHI YOSHIO1, TAKEDA KOJI2, IMANISHI MASAHITO1 1Department of Nephrology and hypertension, Osaka City General Hospital, Japan; 2Department of Clinical Oncology, Osaka City General Hospital, Japan A 68-year-old man who had lung cancer was admitted due to progressive renal dysfunction. Adenocarcinoma of the lung had been diagnosed 15 months earlier.

However, in contrast to ALS, the number of Gems does not decrease in the spinal motor neurons in other motor neuron diseases.[34] Thus, in human spinal motor neurons, the nonspecific alteration of Gems resulting from the suppression of transcriptional activity is less likely. Therefore, we speculate that the alteration of TDP-43 directly decreases the number of Gems. Another important question is how TDP-43 is associated with the formation of Gems. Two hypotheses have been proposed for the formation of nuclear bodies: (i) ordered assembly

LY2157299 research buy of the component proteins; or (ii) stochastic assembly, in which component proteins accumulate in an unordered manner at specific RNA or the complex of core proteins.[27-29, 44, 45] Although the process of how nuclear bodies are formed remains unclear, there are several indispensable find more component

proteins in each body. Thus, two possible molecular mechanisms exist for decreasing the number of Gems by depletion of TDP-43: (i) the depletion of TDP-43 alters the mRNA of the component proteins of Gem; or (ii) TDP-43 directly contributes to the formation of Gems, such that its depletion results in fewer Gems. With regard to the first possibility, it has been reported that TDP-43 regulates the alternative splicing of SMN. The depletion of TDP-43 increased the SMN splicing variant excluding exon 7 in a reporter system.[46] The SMN excluding exon 7 is less stable than SMN with exon 7, resulting in less SMN product.[47] Indeed, we found that the amount of SMN proteins decreased due to the depletion of TDP-43.[34] However, we were unable to confirm the increase in the SMN splicing variants excluding exon 7 in intrinsic SMN mRNA by depletion of TDP-43. Instead of the alteration of splicing variants, we found that the SMN mRNA decreased in the

cells with depleted TDP-43, suggesting that the depletion of TDP-43 induces additional splicing, and the splicing isoform may be less stable than canonical SMN mRNA. However, we were unable to detect the additional splicing variants, which may contribute to the reduced amount of SMN mRNA. Moreover, researchers have not fully evaluated whether the SMN protein Tacrolimus (FK506) or mRNA are reduced in tissues affected with ALS.[48] Therefore, although the intrinsic SMN protein is reduced in cultured cells with the depletion of TDP-43, it is not clear that this is the mechanism underlying the reduction of SMN in tissue affected by ALS. Next, we hypothesized that TDP-43 binds to the component proteins of Gem and increases their stability. Indeed, the protein–protein interaction between TDP-43 and SMN has been reported in a forced expression system,[9, 37, 49] although the result is controversial.[34] In addition, comprehensive analysis of binding proteins to TDP-43 using mass spectrometry failed to identify SMN or other component proteins of Gem.

Recently, a study on Leishmania donovani-infected hamsters has demonstrated a role for TGF-β in induction of lymphocyte apoptosis (45). Regarding the obtained data, no considerable amount of TGF-β has been detected in cell culture supernatants of asymptomatic carriers in comparison with nonhealing cases, and in both study groups, there was no significant difference learn more in the level of TGF-β between uninfected and infected neutrophils. We, therefore, do not think that TGF-β produced by neutrophil has a major impact failure to cure human leishmaniasis.

We here showed that in vitro-infected neutrophils from nonhealing individuals produce a considerable levels of TNF-α, but not TGF-β over background when stimulated with L. major. These results are in line studies demonstrating that TNF-α mRNA production is significantly higher in Leishmania-infected dogs than in controls (46,47). In conclusion, our observations suggest that in the presence of GM-CSF, neutrophil response to CpG-containing DNA sequences may enhance neutrophil response EX-527 to Leishmania infection. The neutrophil activation was more effective in the asymptomatic group as compared to nonhealing group. The molecular aspects of this activation system remain to be elucidated and might be interesting to further expand

the data in view of neutrophil extracellular traps contribution in these groups. Induction of NETs and release of antimicrobial components may contribute to the killing of Leishmania parasites before they are engulfed by professional phagocytes (48), although different strains and species of Leishmania induce NET release in a time- and dose-dependent manner (16). In addition, we assessed basal expression levels of three functional human TLR, TLR2, TLR4 and TLR9, and were able to associate nonhealing Leishmania infection with increased expression of TLR 2, 4 and 9 in neutrophils. Our results suggest that innate recognition

of Leishmania may be incrementally hypersensitized during the development of leishmaniasis. Given that TLR pathways initiate and maintain inflammatory responses (18), the increases in TLR expression may be new associated with the enhanced pro-inflammatory signalling, e.g. TNF-α production, seen in nonhealing subjects. An increase in TLR expression in these subjects may serve to increase innate sensing and responsiveness of the immune system and act as a primary driver for immune activation and disease progression. Experimentally, it has been shown that both TLR4 and TLR9 knockout mice are resistant to parasite-induced damage to the intestinal mucosa, and this is associated with decreased levels of pro-inflammatory cytokines (49). We would like to thank the participation of such nice people that let us sample their blood.

The group log10 PRRSV RNA means were not significantly different among the PRRSV-inoculated groups (data not shown). Macroscopic lesions were characterized by lungs that failed to collapse, were a mottled tan color, and had variable

amounts of cranioventral tan consolidation (particularly in pigs infected with PRRSV). click here The group mean gross lesion scores are summarized in Table 2. Interestingly, the IM-PCV2-PRRSV-CoI group had a lower mean group lung lesion score than the IM-PCV2-I and IM-PRRSV-I groups; however, this was not statistically significant. Lymph node sizes ranged from normal to double in size without differences among groups. Microscopic lung lesions were characterized by mild-to-moderate, focal-to-multifocal interstitial pneumonia characterized by type 2 pneumocyte hypertrophy and hyperplasia Paclitaxel supplier and increased numbers of lymphocytes and macrophages in the alveolar septa. In general, the lesions appeared to be in the resolving stages. Lymphoid lesions were characterized by mild-to-severe lymphoid depletion of follicles and histiocytic replacement of primary or secondary follicular nodes in lymph nodes, tonsil,

and spleen. PCV2 antigen was not detected in any of the non-PCV2 challenged pigs. The prevalence of PCV2 IHC positive animals was as follows: PCV2-I, 3/7; PRRSV-PCV2-CoI, 5/7; IM-PCV2-I, 1/7; IM-PCV2-PRRSV-CoI, 4/7; PO-PCV2-I, 5/7; and PO-PCV2-PRRSV-CoI, 1/7. Mean group PCV2 IHC scores are summarized in Table 2. In general, PCV2-associated lesions were mild (overall lymphoid score range 0 to 3) in IM-PCV2-I and the IM-PCV2-PRRSV-CoI

groups, mild-to-moderate (overall lymphoid score range 0 to 6) in PO-PCV2-I and PO-PCV2-PRRSV-CoI and PCV2-I groups and mild-to-severe (overall lymphoid score range 0–8/) in the PCV2-PRRSV-CoI group. The mean group overall lymphoid scores are these summarized in Table 2. Interestingly, the PO-PCV2-I group had a higher overall lymphoid score and a higher mean PCV2 IHC score compared to PO-PCV2-PRRSV-CoI group; however, this was not statistically significant. An inactivated chimeric PCV2 vaccine (37) was one of the first products licensed for use in growing pigs (Suvaxyn PCV2, Pfizer Animal Health). All of the available commercial PCV2 vaccines to date are inactivated or subunit products and require one or two doses administered IM. While commercially available vaccines have been proven to be efficacious (31–34), the current products have some disadvantages, including the cost of the products and the labor required for administration. There is also increasing concern that currently available PCV2 vaccines may be becoming less effective over time in some herds. The primary objective of this study was to compare the efficacy of IM and PO routes of vaccination using an experimental live-attenuated chimeric PCV2 vaccine in a PCV2b-PRRSV dual-challenge model.

aureus had lower anti-Map antibody titers than noncarriers. As an association of a chronic carrier status and the humoral anti-Eap response was not the goal of our study, we did not examine for a putative carrier status in our cohort, and therefore, in our study, an influence of carrier status cannot be excluded. Of note, in the study by Dryla and colleagues, serum sampling was performed at an early stage

of infection (2–8 days after the onset of disease), with the induction of IgG probably being not fully elicited, and in addition, an antigen was used that did not correspond to full-length Map/Eap (Hussain et al., 2008). Previous studies showed that antibodies against a number of antigens can confer a certain benefit against S. aureus diseases as demonstrated in animal models (Lee et al., 1997; McKenney et al., 1999). However, to date, most trials for a commercial utilization in

humans have failed to confirm clinical efficacy selleck chemical (Deresinski, 2006). Dissemination and invasion of tissue by S. aureus is mainly controlled by complement-mediated opsonization and phagocytosis (Cunnion et al., 2003) accountable for the higher risk of invasive infections in patients with deficiencies in neutrophil functions (Spickett, 2008). Using fluorescent microsphere beads as a surrogate parameter for staphylococci, we could show that, even in the absence of any opsonizing antibodies, the presence of Eap-stimulated phagocytosis by monocytes/macrophages as well as granulocytes. Although the addition of antibodies enhanced uptake moderately, Cabozantinib Selleckchem Temsirolimus most importantly, the level of anti-Eap antibodies did not correlate with the amount of phagocytosed beads. These data indicate that anti-Eap antibodies do not enhance phagocytosis. As patients with severe infections were found to harbor high levels of anti-Eap antibodies, it may therefore be suggested that these antibodies do not prevent invasive infections, but may rather result from such. On the other hand, certain effects of Eap investigated in mice led to the possibility of the use of this molecule for the prophylaxis and/or the treatment of disease such

as autoimmune disorders or cancer (Xie et al., 2006; Schneider et al., 2007; Wang et al., 2010). Our current observation, i.e. the presence of anti-Eap antibodies in every adult, but not in mice, now raises an aspect of caution as it has not yet been determined whether specific antibodies could interfere with these putatively beneficial effects for the host. The ubiquitous presence of anti-Eap antibodies in patients and healthy individuals, however, clearly underlines the pre-eminent role both of Eap and of anti-Eap antibodies in the human response against S. aureus. Our special thanks are due to all patients who consented to participate in this study. Furthermore, we would like to thank Karin Hilgert and Sandra Schmitz for excellent technical support.