Although the HR frequency was often improved when hygromycin B was used for selection of transformants, the difference in frequency was estimated to be less than 10% in favor of the hph cassette by comparison of disruption experiments on the tnr locus using both markers (14, 23). With regard to selectable markers, the higher HR frequency in the TmLIG4-disruptant indicates that

the NHEJ pathway in T. mentagrophytes is mainly dependent on TMKU80-TMLIG4. This finding is supported by the crucial role of Lig4 in the nonhomologous integration pathway in other fungi (12, 40). Moreover, this demonstrates the importance of TmLIG4-disruptants as recipients in gene targeting experiments Fostamatinib for future genetic studies of the dermatophyte T. mentagrophytes. Similarly to other fungal species, the transformation frequency in the TmLIG4Δ mutant was lower than that in the wild-type cells (less than twofold). The subtle reduction in transformation frequency may be attributable to the long homologous sequence stretches. The HR frequencies in the TmLIG4 disruptants did not reach 100% for the four loci, despite the long homologous sequence stretches (Table

2). These results are consistent with those of gene targeting experiments in Pichia ciferrii (40). HR efficiency was Buparlisib order enhanced from 1% in the wild-type to 87% in the Pclig4 (lig4) disruptant (40). In contrast, disruption of mus-53 (lig4) in N. crassa results in an HI frequency of 100%, even when homologous flanking fragments are shorter than 500 bp (12). Moreover, it has been anticipated that the NHEJ pathway would be controlled

mainly by the MUS-52 (KU80 in yeast)-dependent pathway, Baricitinib and partially by the MUS-52-independent pathway, and that both require MUS-53 for the final step of the non-HR pathway (12). In A. oryzae, five of the seven inactivated loci using LigD-deficient host cells have an HR rate of 100% (13). Therefore, it is likely that an additional minor TMLIG4-independent pathway contributes to control of nonhomologous integration in T. mentagrophytes. However, another scenario can be also speculated. In this study, the disruption constructs contained either the nptII cassette (to disrupt the TmLIG4 locus) or the hph cassette (to disrupt the other four loci). Due to limitations in genetic manipulation tools, both cassettes contained the same promoter Pch (685 bp) and terminator TtrpC (573 bp) (Figs 1, 4). Thus, each of the four loci disruption constructs were attracted by two pairs of homologous regions in the TmLIG4 Δ mutants: (i) homologous flanking fragments of about 2 kb to disrupt the gene of interest; and (ii) about 600 bp of homology resulting from use of the same promoter and terminator in the selection cassettes. Because long homologous fragments are preferred for HI, the majority of integrations occurred in the locus of interest. Accordingly, less than 100% HR frequency may be observed in TMLIG4-deficient strains.

The number of isolates of various viruses detected in public health laboratories all over Japan is available in the Infectious Agents Surveillance Report, Japan, for each year since 1981, the data between 1980 and 1991 being documented in published supplements (7, 8). All annual data are available from the NESID system (14). This NESID system database includes the data from Yamagata described in this study.

Several previous studies have reported that HPIV1 infections have clear outbreaks in autumn, mostly in September and November, either every two years (15–18) CB-839 in vitro or at irregular intervals (19). In this study, we found no clear seasonality for HPIV1 infections, although HPIV1 infections did appear to be more common in odd-numbered years. In Japan, no source, including the NESID system, has indicated a seasonal pattern in HPIV1 infections (5–8, 14). In comparison to the clear seasonality of HPIV1 and HPIV3 outbreaks, smaller yearly or irregular outbreaks of HPIV2

have reportedly occurred in autumn (15–19). In this study, we recovered many HPIV2 isolates in the autumn-winter season, observing a particular increase in even-numbered years since 2004 in Yamagata, Japan. The NESID system data support this trend: in the years prior to 1986, HPIV2 infections occurred more commonly in even-numbered years, apart from 1981 and 1983 CP-690550 (7, 8, 14). Thus, HPIV2 infections have commonly occurred in the autumn-winter season every two years in Japan, although this seasonality is less clearly observable than that of HPIV3. In this study from 2002 to 2011 in Yamagata, Methane monooxygenase Japan, we found HPIV3 infections to be grouped in clear

yearly seasonal outbreaks, mainly between May and July. The data in the NESID system also show that HPIV3 infections have peaked in the spring-summer season since 1980 (7, 8, 14). Many previous studies have reported that HPIV3 causes yearly outbreaks, mainly in the spring-summer season, around the globe (15–20); the clear seasonality of HPIV3 in Yamagata appears similar to that observed in other areas. It is generally accepted that HPIV3 as well as RSV infections are common in infants and young children, whereas HPIV1 and HPIV2 infections tend to be commoner in older persons (1–3, 15, 19). Knott et al. reported that the age distribution of HPIV3 infections peaks at 6 months–2 years of age, whereas HPIV1 and HPIV2 peak at 2–5 years (15): findings that are similar to our observations in this study. Clinically, fewer of our patients were diagnosed with croup (2.3–8.2%) than was reported by Knott et al. (9–45%) (15). However, both studies supported the contention that HPIV1 and HPIV2 are more strongly associated with croup than is HPIV3, which is in agreement with the trends described in various textbooks (1, 3). This study indicates that the annual isolation frequencies of HPIV1–3 are 1.6–10.

[25]. Our results indicated that dysregulation of IL-10 and its

receptor in CD4+ and CD8+ T cells may play an important role learn more in the pathogenesis and development of LN, a particular subtype of SLE, but not in all SLE patients. T cells are thought to play a central role in the regulation of the immune system. They activate B cell functions, including the production of autoantibodies, and initiate renal disease by increasing intrarenal nephritogenic cytokines [26–28]. Simultaneous blockading of the B7/CD28 and CD40/gp39 co-stimulation pathways could produce beneficial effects in murine lupus [29]. With regard to the effects of IL-10 on T cells, studies have proved that IL-10 administration results in the direct and indirect inhibition of T cell functions [30–33]. IL-10 administration was also reported to convert responder T cells into IL-10 producers, acting to suppress inflammatory responses [34]. In addition, some studies have demonstrated that IL-10R1 expression plays a critical role in determining whether cells respond to IL-10 [35–37]. AZD6244 mw Because we found that IL-10R1 expression levels on CD4+ T cells and CD8+ T cells were correlated negatively with SLE disease activity, and the STAT-3 phosphorylation of PBMCs upon IL-10 stimulation were delayed and down-regulated

in LN and active patients, we hypothesized that IL-10R expression and signalling down-regulation may lead to a poorer response of effector T cells to the inhibitory signals of IL-10. These effects could result

in T cell activation, followed by initiation or enhancement of autoimmune pathogenesis in LN patients. However, the mechanisms Ergoloid of IL-10R1 expression and signalling down-regulation in CD4+ and CD8+ cells are not yet clear. In this study, we found a negative correlation between plasma IL-10 and IL-10R1 levels on CD4+ and CD8+ T cells. A previous study has shown that the expression of IL-10R1 mRNA was down-regulated after activation in some human T cell clones [38]. These results indicated that circulatory IL-10 and its receptor on T cells may have some regulatory effect on each other. In Caucasian populations, IL-10R1 sense polymorphisms S138G and G330R were proved to be loss-of-function alleles, which could influence IL-10-induced STAT-1 and STAT-3 activation, and G330R may possibly contribute to RA or SLE disease susceptibility [39,40]. However, in the Han populations of China, we have detected IL-10R1 sense polymorphism within exon, but found no contribution to SLE susceptibility (data not shown). Therefore, further research is required to elucidate the mechanism of IL-10R1 expression and signalling down-regulation in CD4+ and CD8+ T cells in LN patients, and to elucidate whether the down-regulation of IL-10R1 expression is a pathogenic factor or a result of an abnormal phenotype.

WZW is the corresponding author. All authors read and approved the final manuscript. The authors declare that they have no competing interests. “
“Although periodontal tissue is continually challenged by microbial plaque, it is generally maintained in a healthy state. To understand the basis for this, we

investigated innate antiviral immunity in human periodontal tissue. The expression of mRNA encoding different antiviral proteins, myxovirus resistance A (MxA), protein kinase R (PKR), oligoadenylate synthetase Ibrutinib research buy (OAS), and secretory leukocyte protease inhibitor (SLPI) were detected in both healthy tissue and that with periodontitis. Immunostaining data consistently showed higher MxA protein expression in the epithelial layer of healthy gingiva as compared with tissue with periodontitis. Human MxA is thought to be induced by type I and III interferons (IFNs) but neither cytokine type was detected in healthy periodontal tissues. Treatment in vitro of primary human gingival epithelial cells (HGECs) with α-defensins, but not with the antimicrobial peptides β-defensins or LL-37, led to MxA protein expression. α-defensin was also detected in healthy periodontal tissue. In addition, MxA in α-defensin-treated HGECs was associated with protection against avian influenza H5N1 infection and silencing of the MxA gene using MxA-targeted-siRNA abolished this antiviral activity. To our knowledge, this is the first study to uncover

a novel pathway of human MxA also induction, which is initiated by an endogenous antimicrobial peptide, namely α-defensin. This pathway may play an important role in the first line of antiviral Tyrosine Kinase Inhibitor Library defense in periodontal tissue. Periodontal tissue is a tooth-supporting structure, which includes gingiva, periodontal ligaments, cementum, and alveolar bone. Chronic inflammation of the periodontal tissue, periodontal disease, is one of the most common inflammatory diseases in humans. The advanced form of the disease, periodontitis, with severe bone destruction may cause tooth loss. The etiologic importance

of bacteria in periodontal disease has been well recognized. Bacterial plaque biofilms continually form on the tooth surfaces adjacent to gingiva. Recent studies have proposed that viral co-infection could enhance the development and progression of periodontitis [[1, 2]]. Detection of herpes simplex virus (HSV) types 1 and 2, human cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV), have been reported in dental plaque biofilm, gingival crevicular fluid, and periodontitis tissue specimens [[3]]. In healthy periodontal specimens, some viral deoxyribonucleic acid (DNA) can also be found, but generally at lower levels than in periodontitis [[4-6]]. Even so, the precise role of viruses in periodontal disease remains unclear. Periodontal tissue is continually exposed to bacterial plaque; therefore an effective innate immune response is critical to maintain homeostasis.

Recently, the delineation of human memory B cells by expression of CD27 has been challenged by the characterization of CD27-negative B cells (IgD-CD27-), indicating molecular imprints

of memory B cells (somatic hypermutation and immunoglobulin class-switch) [9,10]. Plasmablasts or plasma cells can be identified readily by an increased expression of CD38 and CD27 compared to memory B cells. The most immature peripheral B cell population in humans has been characterized in detail recently by the concomitantly high expression of CD24 and CD38 [11–13]. A CD21lowCD38low B cell subset has been shown to be expanded in autoimmune diseases and immunodeficiencies [14–16]. Recently, this B cell population has been selleck compound characterized

as tissue homing, innate-like B cells, containing autoreactive unresponsive B cell clones [16,17]. Using these flow cytometric approaches, changes in the peripheral buy Pritelivir B cell pool have been documented to take place at distinct differentiation stages according to the underlying diseases. Several autoimmune diseases are characterized by an expansion of plasmablasts/plasma cells in the peripheral blood, indicating aberrant B cell development and activation [18]. In contrast, impairment of central or peripheral B cell development takes place in several immunodeficiencies [1,14]. Of interest, B cell regeneration after stem cell ADAMTS5 transplantation or B cell-depleting therapies seems to follow a tightly regulated chronology of B cell reappearance [12]. However, age-dependent reference values for distinct B cell

populations are reported only rarely [19,20]. Therefore, we analysed and quantified different peripheral B cell populations in a cohort of individuals ranging from neonates to adults and tried to establish age-dependent reference values for distinct peripheral blood B cell populations, which can help in the characterization of impaired or disturbed peripheral B cell development. Between November 2007 and August 2009 221 healthy individuals aged 1 month to 50 years were enrolled in this study. The group of healthy individuals consisted of children who were referred to the out-patient clinic at the Children’s Hospital of the University of Würzburg for diagnostic blood testing. Immunological, infectious or haemato-oncological diseases were ruled out in these children. Most of the individuals underwent routine blood testing before minor surgical or diagnostic procedures. Additionally, healthy medical students as well as employees of the University Hospital Würzburg donated blood samples on a voluntary basis. The study was reviewed by the ethics committee of the University of Würzburg and was performed according to the modified declaration of Helsinki. Venous blood was collected, anti-coagulated with ethylenediamine tetraacetic acid (EDTA) and processed within 24 h.

The mock-immunized group that received an AJ challenge were reduced to two mice in the group because of a technical error during challenge. The resulting blood-stage infections were followed by microscopic examination of Giemsa’s solution-stained thin blood smears taken daily using venous blood from the tail. In order to determine the day at which parasites first became detectable in the blood, at least 10 000 red blood cells were examined per smear. For the generation of sporozoites, Anopheles stephensi mosquitoes were allowed to feed on anaesthetized mice that had been inoculated with 1 × 106 iRBCs IP 6 days

previously. Prior to feeding, mouse blood was checked for https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html the presence of gametocytes, and their viability assessed by the observation of exflagellation of microgametocytes in fresh blood Doxorubicin preparations. Seven to 10 days post-feed, mosquito mid-guts

were dissected and the presence of oocysts confirmed. Sixteen days post-feed, mosquito salivary glands were dissected into a 50 : 50 solution of FCS and Ringer’s solution, crushed in a glass and Teflon tissue homogeniser, and the numbers of sporozoites in the homogenate assessed by counting with a haemocytometer. In order to assess sporozoite viability, only those sporozoites displaying circular gliding motility were considered viable. There were no discernable differences in the viability of CB and AJ sporozoites, and sporozoites of both strains were handled in exactly

the same manner prior to immunization and challenge inoculation. All mice were kept on 0·05% para-aminobenzoic acid (PABA)-supplemented water ad libitum and were housed at 21°C on a 12 h-light–dark cycle. Anopheles stephensi mosquitoes were fed with 0·05% PABA-supplemented 10% glucose solution and were housed at 27°C and 70% humidity on a 12-h light–dark cycle. We used R version 2·7·0; The R Foundation for Statistical Computing; http://www.R-project.org) for data analysis. To analyse patterns of parasitaemia during infections, we used mixed effects models because, by treating each infection as a ‘random’ effect, we can account for repeated measures from each infection and overcome pseudoreplication problems associated with such data. These clonidine models were fitted with Poisson error distributions and minimized following stepwise deletion of the least significant term, using log-likelihood ratio tests to evaluate the change in model deviance, until only significant terms remained. We present F-ratios for fixed effects remaining in minimal models. Mann–Whitney tests were used to compare patency data. Cumulative, summary data were analysed with linear models, using anova (F ratios) to evaluate significance of terms. The days on which parasites became detectable by microscopy (patent) in the blood of mice subjected to various immunization and challenge regimens are shown in Table 1.

The aetiology and physiopathology of vitiligo has been discussed widely for several years; however, several findings and clinical observations suggest strongly that vitiligo is an autoimmune-mediated disease, where melanocyte-specific reactants seem to play

a pathogenetic role [1-9]. Serum antibodies to melanocyte-associated antigens are found in the vast majority of patients, while their presence in healthy subjects or patients with other skin disorders is somewhat uncommon [10-14]; some patients suffering vitiligo have other autoimmune conditions [7-9], mainly endocrine autoimmune diseases, and last, but not least, the use of topical or systemic Selleck AZD3965 immunosuppressive therapy results in clinical improvement

of the disease [15-17]. CH5424802 cell line The autoimmune aetiology of vitiligo neither excludes nor is excluded by other aetiopathogenic mechanisms, such as psychological or neurological factors, as it is accepted increasingly that neuroimmunoendocrine networks might play a key role in many physiological and pathological situations [18]. The pathogenetic role of serum antibodies to melanocytes is supported not only by their presence in almost all vitiligo patients, but also in the recent demonstration by ourselves [10] that the titres of such antibodies are found to correlate with the clinical activity of the disease. In fact, the increase in relative amounts of melanocyte-specific serum antibodies, detected

by an enzyme immunoassay, predicts clinical progression of the disease, while the PtdIns(3,4)P2 decrease or stability of such amounts is associated with quiescence of the morbid process. Moreover, in-vitro experiments have demonstrated clearly that melanocyte antibodies are capable of triggering apoptosis of cultured melanocytes, and immunochemical studies show that residual melanocytes in skin biopsies from active lesions display molecular markers of apoptosis [1]. Antibody-mediated immune damage involves manifold mechanisms; in the case where autoantibodies are directed to intracellular antigens – as in the case of vitiligo – it has been demonstrated that certain antibodies of the immunoglobulin (Ig)G isotype are capable of penetrating into cells and reach their respective antigens in living cells [1, 19-26]. One of the many consequences of this phenomenon is the occurrence of apoptosis, triggered apparently by both the programmed and the neglect pathways [20-25]. Altogether, these findings are consonant with the hypothesis that IgG antibodies directed to intracellular melanocyte-related antigens, are capable of penetrating into melanocytes and trigger their cell death by apoptosis, thus resulting in the loss of these cells without an acute inflammatory response.

25 μg/106 cells/mL). The next day, cells were washed to eliminate possible excess of unbound IgE, resuspended in 50 μL of fresh medium without IL-3 and placed at 37°C. For desensitization, cells were treated as per Table 1 (rapid desensitization protocol), and 10 min after the last DNP-HSA addition, placed on ice for β-hexosaminidase release assay. For activation, cells were challenged with 50 μL of DNP-HSA at 20 pg/μL (1 ng DNP) and for control, with 50 μL of HSA at 20 pg/μL

(1 ng HSA), and after 10 min, placed on ice for β-hexosaminidase release assay. β-Hexosaminidase release assay was performed as previously described 16. OVA antigen: Same described method used for DNP antigen, but with overnight sensitization

www.selleckchem.com/products/sch772984.html performed with murine post-immunization serum with OVA-specific IgE (0.25 μg/106 cells/mL) (anti-OVA IgE). For activation, 50 μL of OVA at 200 pg/μL (10 ng OVA) was used. RXDX-106 manufacturer For control, 50 μL of OVA at 200 pg/μL was added to cells without anti-OVA IgE overnight incubation. For specificity experiments, cells were sensitized overnight with 0.25 μg/106 cells/mL of both anti-DNP IgE and anti-OVA IgE. After cells were desensitized or challenged with DNP or HSA, we treated them with 100 ng of rat anti-mouse IgE (clone R35-72 from BD Pharmingen). For control, cells incubated overnight with or without anti-DNP IgE were also treated with 100 ng of rat anti-mouse IgE. Desensitized, non-desensitized and non-IgE treated cells were washed and resuspended in HBSS containing 1 mM CaCl2, 1 mM MgCl2 and 0.1% BSA (Buffer A). Cells were then loaded with 2.5 μM Fura-2AM (Molecular Probes) in the presence of 2.5 mM probenecid for 30 min at 37°C. After being labeled, cells were washed and resuspended in cold Buffer A (0.5×106/mL). Fluorescence output was measured with excitation at 340 and 380 nm in the F-4500 Fluorescence Spectrophotometer (Hitachi), and the relative ratio (R) of fluorescence emitted at 510 nm was Thiamet G recorded. For all fluorescence ratios to start

at zero, the first fluorescence value of each sample was subtracted from all its subsequent fluorescence values. After desensitization or challenge, cell supernatants were collected and LTB4, LTC4 and 12-HHT were measured by RP-HPLC following a published protocol 33. Briefly, samples were applied to a C18 Ultrasphere RP column (Beckman Instruments) equilibrated with a solvent consisting of methanol/ACN/water/acetic acid (10:15:100:0.2, v/v), pH 6.0 (Solvent A). After injection of the sample, the column was eluted at a flow rate of 1 mL/min with a programmed concave gradient to 55% of the equilibrated Solvent A and 45% of Solvent B (100% methanol) over 2.5 min. After 5 min, Solvent B was increased linearly to 75% over 15 min and maintained at this level for an additional 15 min. The UV absorbance at 280 and 235 nm and the UV spectra were recorded simultaneously. PGB2 was used as an internal standard.

Case: A 44-year-old female was admitted to our hospital because of thrombocytopenia and hemolytic anemia. She was diagnosed as SLE twelve years ago and has been treated with immunosuppressive agents, while she experienced a relapse six years ago by lupus nephritis (class III+V). Six months ago she presented with pleurisies and was treated with an increased dose of prednisolone (30 mg/day), which was then gradually tapered to

10 mg/day. The hemoglobin and platelet counts was 6.0 and 200,000/ml, respectively, two weeks before admission, but just after prednisolone was tapered to 8 mg/day, she suddenly presented with thrombocytopenia (16,000/ml), hemolytic Neratinib anemia with schistocytes and hematuria/proteinuria with eGFR mildly declined (25.3 ml/min/1.73 m2). The ADAMTS13 activity was below 5% with a positive anti-ADAMTS13 antibody, while the activity of SLE at that time was considered low based

on unremarkable clinical findings and normal titers of serum complement and anti-nuclear autoantibody. She was diagnosed as TTP associated with SLE and steroid pulse therapy by intravenous methylprednisolone was immediately initiated, followed by oral administration see more of prednisolone (60 mg/day). The platelet count was dramatically improved over 200,000/ml within two weeks and hematuria/proteinuria ameliorated without introduction of plasma exchange. Renal biopsy revealed

mild endothelial RANTES cell swelling and the detachment of endothelial cells from the glomerular basement membrane, suggesting the presence of endothelial injury compatible with thrombotic microangiopathy. Discussion and Conclusion: This is a rare case of TTP in a patient with SLE in remission that was successfully treated with glucocorticoid without plasma exchange, suggesting that early immunosuppressive therapy may be useful for patients with TTP secondary to autoimmune disease when renal involvement remains relatively mild. HANDAJANINGRUM ITA MURBANI, NURAINI AYUDIAH, PARTININGRUM DWI LESTARI, LESTARININGSIH LESTARININGSIH, CHASANI SHOFA, ARWANTO ARWEDI Indonesian Nephrologis Association (Pernefri) Introduction: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease caused by immune dysregulation and affects essentiallyall organ systems in the body. Renal disease is observed in most patients with SLE at some point in the course of their disease and nearly 50% of all patients with SLE develop renal disease in the first year of diagnosis. Renal biopsy in patients with SLE and any clinical evidence of renal disease is important for diagnosis and further management.

Cells were harvested the next day for flow cytometric analyses. Supernatants were collected and stored at −80°C until analysed by infrared array. Monocyte-derived macrophages were washed at the end of 7 days and replenished with fresh medium. Cells were then either stimulated with hBD-3 or incubated in medium alone overnight.

Culture supernatants were harvested and stored at −80°C until analysed by infrared chemokine array. Cells were harvested with ice-cold PBS and gently scraped. The recovered cells were analysed by flow cytometry. Monocytes were stained with antibodies reactive to CD14, CD80 and CD86. Propidium iodide (PI) was used to assess viability. Propidium iodide (10 μg/ml) was added to cells 10 min before analysis. selleck screening library Cells were examined on an LSRII flow cytometer. Searchlight IR custom Array kits were used for multiplex infrared analyses (Aushon Biosystems, Billerica, MA). Briefly, chemokine capture antibodies were spotted to the bottom of 96-well plates. Fifty microlitres of supernatants or standards were added to 96-well plates and non-bound proteins were washed away after 3 hr incubation at room temperature. Secondary biotinylated detecting antibodies were added and incubated 30 min at room temperature. Plates were washed

and streptavidin-DyLightTM 800 Fluor was added for 30 min at room temperature. Plates were rotated for the duration of incubations. After another wash, plates were Transferase inhibitor centrifuged and scanned with an Odyssey infrared imager and analysed with Searchlight Array software. Non-parametric paired tests were used to assess differences between chemokine concentrations in supernatants from cells that were stimulated compared with cells incubated in medium alone. Mann–Whitney U-tests were used to compare results with cells from HIV+ and HIV− donors. Analyses were performed with spss software (IBM, Armonk,

NY). To assess monocyte responses to hBD-3, LL-37 or Pam3CSK4, we incubated purified monocytes with these various stimuli in overnight cell cultures and subsequently examined induction of co-stimulatory molecule surface Parvulin expression by flow cytometric analysis. Human BD-3, and to a modest extent Pam3CSK4, induced CD80 expression in monocytes whereas LL-37 did not affect the expression of this co-stimulatory molecule (Fig. 1a). All three stimuli induced CD86 expression, although hBD-3 provided the most pronounced effects (Fig. 1b). As the intensity of CD86 expression among CD86+ cells appeared to be different depending on the stimuli, we further assessed MFI of CD86+ cells in each experimental condition (medium or medium plus various stimulants). Both hBD-3 and LL-37 tended to increase the intensity of CD86 expression above the levels observed in unstimulated monocytes, whereas Pam3CSK4 did not (Fig. 1b). Hence, co-stimulatory molecule expression is differentially modulated by hBD-3, LL-37 and Pam3CSK4 in human monocytes.