The aim of this study was to investigate whether diabetes and insulin resistance affect B-1 cells and their production of natural IgM. We found that diabetic db/db mice have BAY 57-1293 in vitro lower levels of peritoneal B-1a cells and a decreased

IgM response to pneumococcal immunization and TLR-4 activation. Furthermore, our in-vitro studies showed that glucose in high concentrations reduces B-1 cell IgM secretion and differentiation into antibody-producing cells concurrent with proliferation arrest and increased apoptosis. Specific pathogen-free C57BL/6 mice were purchased from Taconic (Skensved, Denmark). For isolation of peritoneal B-1 cells, male and female C57BL/6 mice were fed a normal chow diet. As a model for insulin resistance, 8-week-old male C57BL/6 mice were assigned randomly to a low glycaemic control diet or a high-fat diet (Harlan

Laboratories, Madison, WI, USA) for 12 weeks. On a caloric basis, the low glycaemic control diet contained 16·8% fat, 60·9% carbohydrate and 22·3% protein (3·3 Kcal/g), whereas the high-fat diet contained 60·3% fat, 21·3% carbohydrate and 18·4% protein (5·1 Kcal/g). The diets contained comparable amounts of vitamins and minerals. Male db/db mice and control mice (+/+ or +/db) on a C57BL/6 background from Jackson Laboratories (Bar Harbor, ME, USA), and db/db and wild-type controls (+/+) on a BKS background from Taconic, were maintained on a normal chow diet. For in-vivo assessment see more of the effect of TLR-4 agonist, 10–12-week-old db/db mice (on a C57BL/6 background) and controls Non-specific serine/threonine protein kinase were injected intraperitoneally with 0·34 mg/kg of the TLR-4 agonist Kdo2-Lipid A (Avanti Polar Lipids, Inc., Alabaster, AL, USA) or vehicle. For immunization studies, 10–12-week-old db/db mice and controls (on a C57BL/6 or BKS background) and C57BL/6 mice maintained on diets for 3 months were injected intraperitoneally with 11·5 μg of a 23-valent vaccine (Pneumovax; Sanofi Pasteur MSD, Lyon, France), containing 0·5 μg each of 23 types of polysaccharides from S. pneumoniae

or saline. As indicated for each experiment, body weight, plasma insulin, glucose and antibody titres were followed in longitudinal blood samples. Before blood sampling, mice were fasted for 4 h. Plasma glucose in blood samples from fasted, non-anaesthetized animals was determined with a glucose dehydrogenase method by using HemoCue® B-glucose microcuvettes (HemoCue®, Ängelholm, Sweden) and insulin was determined by a mouse insulin enzyme-linked immunosorbent assay (ELISA) (Mercodia, Uppsala, Sweden). Plasma triglycerides and cholesterol were measured using Konelab 20 Autoanalyzer (Thermo Electron Corporation, Vantaa, Finland). All mice were housed in a controlled environment and all experimental protocols were approved by the animal ethical committee in Gothenburg.

This was made known at various

nationwide meetings. In 2009, service providers for the hemodialysis population were 68.4% at voluntary welfare (charity) organisations, 2.5% public hospitals and 29.1% private facilities. We describe our experience with use of the hotline over years 2011–2012 with a retrospective survey. Methods: Renal coordinators (RCs) receive email or phone calls from DCs nationwide. Cases are triaged by protocol and are referred to a nephrology trainee for discussion with a specialist nephrologist, vascular surgeon or directed to DEM. The coordinator may be asked to assist with further actions. Results: The number of cases handled was 433. Non-SGH cases (n = 6) were removed from analysis. The remaining 427 cases were GSI-IX datasheet from 305 patients aged 62 +/− 10 years of age, Male: Female 2.02:1. Etiology of renal failure included diabetic nephropathy 54.6% (n = 233), chronic glomerulonephritis 25.8% (n = 110), hypertension 13.3% (n = 57), others 6.3% (n = 27). Co-morbidities in these patients included diabetes mellitus 62.8% (n = 268), ischemic heart disease 34.4% (n = 147). Over the two years, 52.4% were unique cases, 27.2% (58 patients) cases referred twice, 20.4% (23 patients) three or more times. Referral sources were National Kidney Foundation 90.6% (n = 387), Kidney Dialysis Foundation 6.3% JNK inhibitor mw (n = 27)

and private DCs 3.1% (n = 13). Access types handled included Arteriovenous fistula 75.2% (n = 321), Arteriovenous graft 22.9% (n = 98) and tunnelled catheters 1.9% (n = 8). Causes of referral included poor access flow 65.6% (n = 280), recirculation 8.0% (n = 34), swollen upper limbs 3.5% (n = 15), high venous pressure

2.1% (n = 9), high access flow 2.4% (n = 10), infected access 2.1% (n = 9), thrombosed access 3.0% (n = 13), other reasons 13.3% (n = 57). The actions taken included early vascular surgery reviews 33.7% (n = 144), elective angioplasty appointments 25.3% (n = 108), continuation with previously arranged vascular appointments 6.6% (n = 28) referral to DEM for admission 7.7% (n = 33), other actions 26.7% (n = 114). Conclusion: The vascular hotline creates a channel for dialysis Y-27632 mouse centres to arrange for early assessments of vascular accesses. However, trained personnel are essential for effective use. UBUKATA MASAMITSU1, AMEMIYA NOBUYUKI2, TAKEI TAKASHI3 1Department of Nephrology, Saiseikai Kurihashi Hospital; 2Department of Nephrology, Saiseikai Kurihashi Hospital; 3Department of Nephrology, Saiseikai Kurihashi Hospital Introduction: Patients with end-stage renal disease under maintenance hemodialysis are prone to malnutrition because of a poor diet and/or uremic complications. There are some reports that dialysis patients are at a high risk for thiamine deficiency, which may be caused by dietary deficiency and/or loss during dialysis, and the complications associated with it, including encephalopathy and beriberi.

05). Conclusion: EPA improves the urinary protein in association with an increase in the EPA/AA ratio in CKD patients with dyslipidemia. EPA may have renoprotective role by reduction of proteinuria in CKD patients. The mechanisms of reduction of proteinuria by EPA would be clarified in the ongoing study. GULATI SANJEEV, KUMAR KAPIL, GUPTA UMESH, HDAC inhibitor drugs KALRA VIKRAM, TIWARI S C Fortis Institute of Renal Sciences Introduction: Interstitial fibrosis &

tubular atrophy is the leading cause of graft loss in kidney transplant patient. Proliferation signal inhibitors may help in reducing calcineurin inhibitor exposure without increasing acute rejection episodes. Current study evaluated efficacy of conversion from mycophenolate to everolimus with CNI minimization in patients with biopsy proven

IFTA and deteriorating renal function. Methods: Prospective single center trial, study cohort selected from 200 live related renal transplant recipients in followup. All had received basiliximab induction and triple drug immunosupression (tacrolimus, MMF/EC-MFS, steroids). Inclusion criteria: biopsy proven IFTA, absence of significance proteinuria (<400 mg/24 hour), progressive graft dysfunction (decline of GFR > 15% buy 5-Fluoracil over 1 month), eGFR > 40 ml/min/1.73 m2. All underwent conversion from mycophenolate to everolimus with CNI minimization. Results: The study group composed of 22 patients (M : F = 19:3), mean age 37 years (range 24–58). Conversion done at 24 months Tangeritin (IQR: 8.5–24.5) post-transplantation and median follow-up is 22 (IQR: 5–9) months. The tacrolimus trough levels decreased from 5.1 ± 1.6 ng/ml to 3.6 ± 1.1 ng/ml (p = 0.03). The everolimus levels achieved were 6.68 ± 2.4 ng/ml and 5.7 ± 1.4 ng/ml at 1 and 3 months. The eGFR that had declined from best stable values of 59.3 ± 11.9 ml/min to 48.2 ± 9.5 ml/min at conversion stabilized and improved to 50.7 ± 11, 53.3 ± 13.1, 54.9 ± 13.9 and 57.1 ± 10.1 ml/min at 1, 3, 6 and 12 months post conversion respectively (p = 0.028 at 3 months). There were no episodes of rejection, 2 patients was withdrawn at 3 months & 24 months due to proteinuria. Conclusion: Conversion from mycophenolate to everolimus

with CNI minimization resulted in stabilization of renal function. OJIMA SAKI, IO HIROAKI, WAKABAYASHI KEIICHI, KANDA REO, YANAGAWA HIROYUKI, AOKI TATSUYA, NAKATA JUNICHIRO, YAMADA KAORI, NOHARA NAO, SHIMIZU YOSHIO, HAMADA CHIEKO, HORIKOSHI SATOSHI, TOMINO YASUHIKO Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine Introduction: Previous study reported that dialysis patients are easy to occur carnitine deficiency. Thus, they have shown the weakness of the skeletal muscle, cardiomyopathy, heart failure and renal anemia. In the randomized controlled trial of L-carnitine in dialysis patients who had dilated cardiomyopathy, the survival rate of the carnitine administrated group was significantly better than the controled group for 3 years (Rizos I.

In G93A mSOD1 mice [75], degeneration of the anterior

horn neurones was noted early on in the disease process [110]. Ultrastructural studies showed membrane bound vacuoles originating from the degenerating mitochondria, via distension of the outer mitochondrial membrane, expansion of the IMS, preceding disintegration of the IMM [56]. The notion of a causal role of this mitochondrial dysmorphology in the pathogenesis of ALS has arisen, due to the observations that these defects occur at a presymptomatic stage in G37R and G93A mSOD1 mice [56]. Furthermore, at the onset of disease symptoms, the dominant pathological event in the ventral horn is a rapid increase in the number of vacuolated mitochondria, Autophagy inhibitor correlating with decline in muscle strength and preceding motor neuronal cell death [56,74,111,112]. It is postulated that this death is due to apoptosis, with the relative density of cytochrome c immunoreactivity noticeably reduced in the swollen mitochondria, suggestive of its pro-apoptotic release into the cytosol [56]. However, over-expression of wild-type SOD1 may also lead to vacuolation of mitochondria [113], and as mitochondrial vacuolation is not seen in all mSOD1 mouse models, it is important to consider whether more subtle disruption of mitochondrial morphology occurs. The initial cause of this mitochondrial

dysmorphology is unclear, although mSOD1 has been implicated in the process, with vacuolation of mitochondria correlating with accumulation of mSOD1 in the mitochondrial IMS of transgenic selleckchem mice [113]. Furthermore, mSOD1 Enzalutamide concentration has been found to be present in only mildly swollen mitochondria, suggesting that the translocation of mSOD1 into the IMS may trigger vacuolation

of the mitochondria, possibly via dysfunctional interaction with mitochondrial chaperones, eliciting structural damage [56,114]. A fragmented network of motor neuronal mitochondria in the anterior horn of SALS patients is suggestive of defective fusion, or an increase in the levels of fission [49]. This is supported by investigation of cultured motor neurones derived from G93A mSOD1 transgenic mice; mitochondria were found to have a lower aspect ratio, suggestive of ‘rounding up’ of individual mitochondria [115]. Furthermore, investigation of a mSOD1 expressing NSC-34 cell line revealed fragmentation of the mitochondrial network alongside remodelling of the mitochondrial cristae [12,116]. Recent analysis of mitochondrial morphology in differentiated NSC-34 cells transfected with IMS-targeted mSOD1 revealed a significant decrease in mitochondrial length, indicative of fragmentation of the mitochondrial network in the presence of mSOD1 [109]. Thus, loss of mitochondrial fusion or an increase in mitochondrial fission may be a component of the pathogenic process in ALS.

A three part questionnaire was developed and administered to collect: (1) demographic information; (2) level of medication awareness; (3) self-reported medication errors; and (4) perception of benefit of a medication card.

The responses were scored to assess medication understanding and perception of a medication card. The data was analysed with SPSS v.22 and P < 0.05 considered significant. Results: 26 out of 34 patients completed the questionnaire with 57% being male and the average age 61.3 (± 11.3) years. Patients took 7.9 (± 3) medications, BAY 73-4506 manufacturer 73.1% of respondents had high school or less education and 38% reported English as their primary language. There was no association between medical comorbidities, level of education or primary language with medication awareness. Women demonstrated better medication awareness than males (58 ± 5 vs 42 ± 5, P < 0.05). There was increasing acceptance of the benefits of a medication card as education level improved (P < 0.05). 15% of patients report an adverse drug reaction in the previous year. Conclusions: There is acceptance for the use of medication cards by HD patients who are subject to polypharmacy and this may improve medication awareness. Women appear to have better medication awareness. 204

INVERSE ASSOCIATION BETWEEN 25-HYDROXY-VITAMIN D CONCENTRATIONS AND SERUM LEVELS OF PRO-ATHEROGENIC CYTOKINES IN CHRONIC Lumacaftor order Calpain KIDNEY DISEASE PATIENTS E ROUSE1,2, K YOUNG 1,2, WH LIM1,2 1Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, WA; 2School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia Aim: To determine the association between novel risk factors for cardiovascular disease (CVD) and circulating pro-atherogenic cytokines and arterial stiffness in chronic kidney disease (CKD) patients. Background: Novel risk factors for CVD including oxidised

low-density lipoprotein (oxLDL) and vitamin D have been implicated in the pathogenesis of CVD in CKD patients. High levels of circulating oxLDL level and 25-hydroxy-vitamin D (25OHD) deficiency are associated with inflammation, increased pulse wave velocity and CVD mortality in the general population and early CKD patients but a similar association has not been consistently shown in pre-dialysis advanced CKD patients. Methods: This was a cross-sectional study of 40 pre-dialysis stage 5 CKD patients recruited from a single-centre. Plasma oxLDL levels (ELISA), 25OHD concentration, interleukin (IL)-12 and 18 (ELISA) and pulse wave velocity (PWV, SphygmoCor® system) were determined at a single time-point. Associations between log-transformed oxLDL (log-oxLDL) and log-25OHD with IL-12/18 and PWV were examined using linear regression analysis. Results: Mean ± SD age was 65 ± 13 years with 72% of male gender.

Protein modified diets of all types lasting a minimum of 4 months were considered

with protein intake ranging from 0.3 to 0.8 g/kg per day. Overall protein restriction appeared to slow progression of CKD, but not by much on average. Individual variability suggests some may benefit more than others. Results of meta analysis imply that patients can delay dialysis by, on average around one or 2 months. Positive SCH 900776 but non-significant correlation between improvement in GFR and level of protein restriction is evident. There were insufficient studies to recommend a level of protein intake. Furthermore, problems of non-compliance remain a significant issue. The review also considered different sources of protein (e.g. red meat, chicken, fish, vegetarian); however, relevant studies are of short duration only. The authors consider that the available information supports further research in this area. The number of studies that include people with type 2 diabetes are limited. The study by Dussol et al.121 was the only other RCT identified that was not reviewed by Robertson et al.120 This 2 year single centre RCT of type 1 and type

2 diabetes indicated that the low-protein diet did not alter the course of GFR or of AER in people with diabetes with incipient or overt nephropathy. Table A6 includes a summary of studies identified by the search strategy. The studies are characterized

by being small and of short duration. Relevant details are provided GSK126 mouse below; however, as for dietary fat, there are insufficient reliable studies that provide evidence to support a recommendation in relation protein restriction in the prevention and management Dimethyl sulfoxide of CKD in people with type 2 diabetes. When considering the evidence related to salt intake and CKD in people with type 2 diabetes, the following points made based on a literature review for preparation of a Cochrane Protocol are noteworthy:122 Dietary salt is important in BP control in both hypertensives and normotensives (supported by meta-analyses) and therefore expect that this could be protective in the development and progression of CKD. Table A7 presents a summary of studies identified by the search strategy in relation to the assessment of the role of restricted salt intake. As for protein restriction the studies are small and of short duration. Details of the studies are included in Table A7; however, it is concluded that there are insufficient reliable studies that provide evidence to support a recommendation in relation to restriction of dietary salt and the prevention and management of CKD in people with type 2 diabetes. Smoking increases the risk of the development and progression of CKD in people with type 2 diabetes (Evidence Level II – Aetiology).

This possibility seemed to be strengthened by the observation

that SIGNR1 physically associates with Dectin-1 constitutively in cells over-expressing SIGNR1 and Dectin-1 (data not shown). Moreover, SIGNR1 and Dectin-1 co-localized to part of the phagosomal membrane in RAW-SIGNR1/Dectin-1 cells (data not shown). This is not the case in rpMϕ, where association/co-localization of SIGNR1 and Dectin-1 was not observed without stimulation, as reported in the case of TNF-α production by collaboration between TLR2 and Dectin-1 8. However, Dectin-1 was recruited to the phagosomal membrane where SIGNR1 captures microbes, and both molecules were detected to physically associate with each other in a time-dependent manner after stimulation. The oxidative burst of RAW-SIGNR1 cells in response to live C. albicans was too weak SCH772984 to detect (data not shown). This may be due to the fact that the cell wall in the live microorganism is covered with mannoproteins, preventing Dectin-1 from accessing the β-glucan ligand. However, RAW-SIGNR1 cells showed significant candidacidal

activity, and this activity was substantially dependent Atezolizumab on Syk-mediated signaling. When RAW-SIGNR1/Dectin-1 cells (data not shown) and rpMϕ were exposed to live microbes, β-glucan appeared to be accessible to Dectin-1, and SIGNR1 and Dectin-1 co-localized to part of the phagosomal membrane. Therefore, it is feasible that such cellular events effectively induce candidacidal activity. Arachidonate 15-lipoxygenase It is not clear how SIGNR1 utilizes Syk-mediated signaling though Dectin-1. It has been reported that cross-linking of SIGNR1 by neo-glycoprotein containing mannose residues and specific antibody induces the activation of JNK and NF-κB, leading to the production of TNF-α 31, IL-12 32 and IL-10 33. Therefore, it is plausible that SIGNR1

transduces the signal by itself. However, RAW264.7 cells expressing the SIGNR1 truncated cytosolic portion were still able to facilitate the oxidative response, suggesting that it is unlikely that there is any direct involvement of the cytosolic portion of SIGNR1 in signal transduction. SIGNR1 in RAW264.7 transfectants is reported to co-localize in lipid rafts with several Src family kinases 31. Therefore, cross-linking of SIGNR1 by ligand/microbes possibly induces activation of the kinases. Alternatively, SIGNR1 might also cooperate with other unidentified molecules than Dectin-1 to induce the Syk-dependent signaling. These possibilities remain to be elucidated in future experiments. In the systemic infection or stimulation, SIGNR1 may not be a major player in the host defense, since SIGNR1 is expressed in limited populations of DCs and Mϕ.

Previous studies have reported that LPS injections prevent diabetes

establishment Dabrafenib in vitro in NOD mice. In the original report, i.v. administration of LPS was initiated at 6 weeks of age, and repeated every week [35]. In a recent work, 3- to 4-week-old mice were treated weekly with 5 μg LPS i.p. [39]. Together these studies indicated that LPS treatment initiated before extensive infiltration of the pancreatic islets is protective. Our data extend these previous results by showing that LPS treatment is also highly effective in preventing progression from late insulitis (12 weeks) to diabetes. Intriguingly, administration of LPS to BDC2.5 TCR transgenic NOD animals precipitated diabetes [54]. In contrast to normal NOD, the vast majority of T cells in the BDC2.5 animals are specific for an islet antigen presented by the MHC class II molecule Ag7. It is likely that in this system the pro-inflammatory effect of LPS prevailed over its tolerogenic action owing to the over-representation of autoreactive cells. Other protective treatments in NOD mice have been shown to elicit distinct and even disparate outcomes, according to the number of engaged diabetogenic cells (e.g. [55]). We showed that LPS administration must be sustained to ensure long-lasting protection of NOD mice. Similar requirement was reported for another bacterial compound,

OM85 [56]. In contrast, a single injection of CFA, an emulsion containing mycobacterium ADAM7 extract, affords life-long protection [32, 33]. As CFA can neither be resolved nor eliminated by the body, it is likely that the selleck compound release of the bacterial compound is actually long lasting. The general principle associated with the ‘hygiene hypothesis’ is that certain infections early in life promote the development of a healthy immune system endowed with robust self-tolerance mechanisms. Yet, the prototypic example of experimental protection of NOD mice by environmental factors

is actually provided by exposure of a NOD colony to either uncontrolled or SPF environment [29, 30]. It would be interesting to test whether, as suggested by human epidemiology studies [29, 30], NOD mice raised in an infectious microorganism-rich environment until young adult age, and only then decontaminated and maintained in an SPF environment would remain protected. LPS tolerogenic effects in vivo are known for long, notably in mismatched graft and in delayed type hypersensitivity [46, 47]; however, the mechanism of action remains elusive. Here, we demonstrate that LPS protects NOD mice from diabetes occurrence through the enhancement of Treg activities. By performing adoptive transfer experiments we formally established that the protection afforded by LPS is mediated by a subset of cells encompassed within the CD25+ subset of lymphocytes.

Results:  Twenty nine patients with a mean age of 10.3 ± 2.6 years were studied. Hypertension, microscopic haematuria and nephrotic-range proteinuria were seen in 66%, 86% and 60% of the patients, respectively. R788 price Forty-one per cent of biopsies showed cellular or fibrocellular crescents. Twenty patients (69%) achieved remission at the end of induction therapy. There were no significant differences in all parameters studied between responsive and nonresponsive groups.

The relapse rate after maintenance therapy was 58.8%. Conclusion:  Our results show that pulse cyclophosphamide is an effective regimen for induction therapy in children with diffuse

proliferative glomerulonephritis. No definite predictor for unresponsiveness was detected in this study. “
“Aim:  Although recent genetic studies suggested that several genetic variants increase the risk for chronic kidney disease (CKD), the genes that underlie genetic susceptibility to this condition remain to be identified definitively. We showed that the CT polymorphism see more (rs6929846) of BTN2A1 and AG polymorphism (rs2569512) of ILF3 were significantly associated with myocardial infarction in Japanese individuals by a genome-wide association study. The purpose of the present study was to examine a possible PIK3C2G association of these polymorphisms (rs6929846, rs2569512) with CKD in Japanese individuals. Methods:  A total of 7542 Japanese individuals from two independent populations were examined: Subject panel A comprised 971 individuals with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min 1.73 m−2)) and 2269 controls (eGFR ≥60 mL/min

1.73 m−2); and subject panel B comprised 1318 individuals with CKD and 2984 controls. Results:  The χ2 test revealed that rs6929846 of BTN2A1, but not rs2569512 of ILF3, was significantly related to the prevalence of CKD both in subject panels A (P = 0.0383) and B (P = 0.0477). Multivariable logistic regression analysis with adjustment for covariates revealed that the CT polymorphism (rs6929846) of BTN2A1 was significantly associated with the prevalence of CKD in subject panels A (P = 0.0422; recessive model; odds ratio, 2.36) and B (P = 0.0386; dominant model; odds ratio, 1.21) with the T allele representing a risk for this condition. Conclusion:  Our results suggest that BTN2A1 may be a susceptibility gene for CKD in Japanese individuals.

2d,h). To study the effect of Leishmania virulence on DC differentiation, we tested the ability of the four Lm clones to interfere with the expression of CD1a, HLA-DR, CD80 and CD86 during DC differentiation. We observed that all tested Lm clones were able to down-modulate CD1a expression significantly when compared with DCs differentiated without parasites (P = 0·002) (Fig. 3). Epigenetics inhibitor No significant

differences were observed between HV and LV Lm clones. We also showed a slight decrease in HLA-DR and CD80 expression as well as a slight increase in CD86 expression in the presence of Lm promastigotes when compared to uninfected DCs, but these results were not significant (Fig. 3). To evaluate the impact of virulence on cytokine production by DCs, the

four Lm clones were incubated with immature DCs for 48 h and IL-12p70, IL-10 and TNF-α production was analysed. We did not observe significant differences in IL-12p70, IL-10 or TNF-α production between Lm-infected DCs and uninfected cells for all tested clones. The effect of virulence of Lm parasites was also analysed on cytokine production buy Kinase Inhibitor Library during IFN-γ-, LPS- or IFN-γ/LPS-induced maturation of DCs. As shown in Fig. 4, highly significant levels of IL-12p70, IL-10 and TNF-α were detected in infected and uninfected LPS or IFN-γ/LPS matured DCs when compared with immature cells. Interestingly, we observed that infected and LPS-matured DCs produced lower levels of IL-12p70 than uninfected LPS-matured DCs, whereas the presence of parasites did not affect IL-12p70 production in IFN-γ/LPS-matured DCs. No IL-12p70 production was detected in infected and IFN-γ-stimulated DCs. These results were observed regardless of Lm clones virulence. We also showed a slight increase of IL-10 production in the presence of all clones except LV and of

TNF-α production in the presence of HVΔlmpdi and LVΔlmpdi clones during LPS-induced maturation of DCs (Fig. 4). In this study, we evaluated correlations between human 3-oxoacyl-(acyl-carrier-protein) reductase DC response and Lm clones that were differentially pathogenic in BALB/c mice. The contrasting pathogenicity of these clones was more pronounced than it was for the isolates from which they were derived. Indeed, unlike the LV isolate that induced mild disease, the LV clone was not able to induce lesions in mice (unpublished data). We showed that infection rate and parasite burden were significantly higher in DCs infected with HV than with LV. Previously, using the wild Lm isolates LmHV and LmlV, we showed a significantly higher parasite burden in LmHV-infected human monocytes, suggesting that the high virulent isolate was able to replicate more rapidly inside the phagolysosome [23]. Here, we extend these observations to human DCs. We showed significant differences in uptake and intracellular growth of Lm clones having different levels of virulence. We also observed a significant decrease in infection rate and parasite burden in HVΔlmpdi-infected DCs compared with HV-infected DCs.