RNA (3 μg) was reverse-transcribed Selleck RG7422 using oligo (dT) 15 primer (Promega) following manufacturer’s instructions. Primers used for the amplification of hamster

Prdx6 cDNA were 5′-ACTTTGAGGCCAATACCAC-3′ and 5′-TGTAAGCATTGATGTCCTTG-3′, and for GAPDH cDNA 5′-AGAAGACTGTGGATGGCCCC-3′ and 5′-TGACCTTGCCCACAGCCTT-3′ (based on GenBank Accession nos NM177256.3 for Prdx6 and DQ403054.1 for GAPDH). To confirm the identity of the PCR product, amplicon was cloned and sequenced (18). Sequence of amplicon and per cent identities with rat, mouse and human homologous sequences are shown in Table 1. Relative mRNA expression was determined using an ABI7500 thermal cycler by SYBR Green assay (19). Each experiment was performed Small molecule library high throughput in triplicate. In brief, PCR reaction solution (20 μL) contained 5 μL of cDNA, PCR buffer, 0·25 mm of each dNTP, 5 pmol of each primer, 0·5X SYBR Green and 1 U of Hot start Taq polymerase (MBI Fermantas, St. Leon-Rot, Germany). PCR thermocycling conditions were 95°C for 10 min, followed by 40

cycles of 95°C for 15 s and 55°C for 30 s and 72°C for 1 min. A dissociation curve was constructed in the range of 60–99°C. All data were analysed using the Rotor Gene 5 software (Corbett, Australia) with a cycle threshold (Ct) in the linear range of amplification and then processed by the method relative to GAPDH mRNA (20). Localization of Prdx6 expression in O. viverrini-infected hamster liver was performed by an immunohistochemical procedure (19). In brief, paraffin sections (5-μm thick) were deparaffinized in xylene and rehydrated in descending gradations of ethanol. To enhance immunostaining, sections were placed in citrate buffer (pH 6·0) and autoclaved at 120°C for 10 min for antigen unmasking. Tissue sections were incubated overnight with rabbit polyclonal anti-Prdx6 antibody (1 : 100; Abcam) at room temperature. Sections were incubated with horseradish peroxidase-conjugated mouse anti-rabbit IgG antibody (1 : 200; Zymed Laboratory) and stained sections were Arachidonate 15-lipoxygenase visualized with 3,3-diaminobenzidine tetrahydrochloride

as a chromogen and haematoxylin was used for counterstaining. Data are presented as means ± SD. The Student’s t-test was used to compare between uninfected and infected groups. Statistical analysis was performed using the SPSS version 11·5, with P value <0·05 considered as significant. Differential patterns of protein expression in hamster livers were identified by two-dimensional gel electrophoresis (2DE) (Figures 1 and 2). On the average, 380–400 protein spots were detected in O. viverrini-infected and uninfected groups. Among them, 250–350 protein spots were successfully matched between infected and uninfected groups, with expression levels of 49 proteins being significantly different between these groups (P < 0·05) (Table 2). O.

The reflex responses were recorded using two surface electrodes located on the cheekbone overlaying the orbicularis oculi muscle, in line with the pupil in forward gaze, to record the response of the muscle. The EMG signal was then conducted to the recording equipment. The reference electrode was placed on the lateral surface

of the nose and a ground electrode was positioned at an electrically inactive site, such as the arm. The EMG amplitude of a single blink is rarely more than a few hundred microvolts; because of this, recording conditions Ixazomib mw should improve the flow of current from the skin surface to the electrodes. Skin was prepared by removing makeup and dead skin cells, to reduce

any impedance between skin and electrode gel. After preparation of the skin, an EMG technician massaged a thin layer of electrode gel onto the recording site. Proteases inhibitor The electrical stimulation of the supraorbital nerve elicits two responses in the orbicularis oculi muscle: the early ipsilateral response, R1, and late bilateral responses, R2. The stimulus lasted for 0.1–0.2 ms and its intensity was set to a 100-microvolt/division and always under the pain threshold, in order to evoke R1 and R2 at the same time as avoiding any activation of nociceptive afferents. The EMG signals were amplified with a frequency response of 20 Hz to 3 kHz, which allowed for accurate analyses of short latency responses. The latency times for both the R1 and R2 were measured from the stimulus artifact to the initial response

of the orbicularis oculi muscle. The subjects had no auditory or visual pre-pulse stimulation. All subjects gave their informed consent for the experimental procedures, which were approved by the local ethics committee and conducted in accordance with regulations laid down in the Declaration of Helsinki. Statistical analysis was performed using Student’s t-test. The software used for all statistical evaluations was PASW 18.0.0 Statistics program (SPSS Inc., eltoprazine Chicago, IL, USA). The mean ages of the patients with OAB and voiding symptoms were 57.31 ± 6.87 and 58.06 ± 6.2 years, respectively. There was no significant difference in the demographic and clinical data of the groups (Table 1). Early blink latency times were similar in both groups, bilaterally. All of the late blink latency times were significantly longer in patients with storage symptoms than among those with voiding symptoms (P < 0.05) (Table 2). Figure  2 represents the latency times for the patients with storage and voiding symptoms, with a 95% confidence interval (as darker bars) and range. This study found a strong association between increases in late blink reflex latency times (R2) and storage symptoms.

To date, only the rudimentary mechanisms of this phenomenon have been identified, but a greater understanding of the mechanisms underlying Treg to Th17 conversion may identify targets for modification and pharmacological intervention that might stabilize Tregs intended for clinical use and inhibit their proinflammatory potential in vivo. There are no conflicts of interest: the authors have been supported by grants from the Medical Research Council and the British Heart Foundation. “
“Human embryos develop at varying rates in culture, with only a fraction of the eggs retrieved

developing to ‘transfer quality’ embryos. We investigated whether the ratios between the High Content Screening number of eggs retrieved or the number of pro-nucleate embryos formed and the number of Day 3 embryos with ≥5 cells [oocyte ‘die-off this website ratios’ (DOR)] were correlated with the chance of IVF success, independent of other factors such as embryo grade score and patient’s age. We also investigated what factors may be correlated with this ratio. 608 IVF fresh cycles in subfertile women were retrospectively evaluated. For each cycle, an oocyte DOR number was calculated as follows: Number of eggs retrieved

divided by the number of Day 3 embryos with ≥5 cells. This number was correlated with the subsequent success rates for the index cycles. A ‘post-fertilization’ or ‘embryo’ die-off ratio (EDOR; the number of pro-nucleate embryos/the number of day 3 embryos ≥5 cells) was also calculated. The oocyte DOR showed a reverse linear correlation with IVF live birth rate. Live birth rate = (−5.75; DOR) +71.6 (with DOR > 1; P ≤ 0.005; R = −0.87). In addition, the oocyte DOR continued to show an inverse correlation with success rates even when embryo quality and patient’s age were held constant. The post-fertilization or EDOR also continued to

show a statistically significant negative correlation with live birth rate (R = −0.91; P ≤ 0.01). The preconception TNF-α:IL-10 ratio, an immmunologic marker (drawn 3.3 ± 2.6 months preconception), was more strongly correlated with high oocyte DOR than either 4-Aminobutyrate aminotransferase age or number of eggs retrieved (P = 0.04, 0.14, 0.72, respectively). When anti-TNF-α therapy (Humira) was given preconception, the oocyte DOR’s negative effect on live birth rate was nearly eliminated (correlation coefficient between oocyte DOR and live birth rate: cycles using no Humira, R = −0.90, P ≤ 0.006; cycles using Humira, R = 0.25, P ≤ 0.55). In subfertile women undergoing IVF, the oocyte DOR may help predict IVF success rates. This factor may offer an additional tool to help improve implantation rate, clinical pregnancy rate, live birth rate, and live birth rate per embryo transferred for an upcoming IVF cycle.

Furthermore,

the associated high mortality and resistance of mucorales to the most widely used antifungal drugs require a thorough identification of the aetiologic agent using molecular tools. This work was carried out, in part, with financial assistance from the Indian Council of Medical Research (ICMR 5/3/3/26/2010-ECD-I), New Delhi, India. J.F.M received grants from Astellas, Basilea and Merck. He has been a consultant to Astellas, Basilea and Merck and received speaker’s fees from Merck and Gilead. All other authors: no potential conflicts of interest. EPZ-6438 The authors alone are responsible for the content and writing of the paper. “
“In 2008, the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) published revised definitions for diagnosing invasive fungal disease. A previous prospective

trial of liposomal amphotericin B for invasive mould disease (AmBiLoad) used modified EORTC/MSG 2002 criteria. We wished to re-evaluate the response and survival based on the revised definitions to compare the outcomes of early vs. late treatment. Patients who had received an allogeneic haematopoietic stem cell transplant or who were neutropaenic (absolute neutrophil count <500 μl−1 within 14 days of study entry) had been recruited on the basis of a halo or air crescent sign on chest computerised tomography. Originally classified as probable invasive mould disease, they were categorised as possible invasive mould disease GDC-0973 in vitro using 2008 criteria. Patients had received liposomal amphotericin B at either 3 or 10 mg kg−1 QD for 14 days, followed by 3 mg kg−1

QD. Response at end of treatment and the 12-week survival were re-calculated according to 2008 definitions. Six-week survival was estimated by Kaplan–Meier analysis. Of 201 patients with invasive mould disease, 118 (59%) had a diagnosis based on halo signs (possible cases). Mycological evidence was present in 83 (41%) cases (probable/proven cases). Survival rates at 12 weeks for possible vs. probable/proven cases in the 3 mg kg−1 QD group Phospholipase D1 were 82% vs. 58% (P = 0.006), and 65% vs. 50% (P = 0.15) in the 10 mg kg−1 QD group. At 6 weeks, rates were 87% vs. 69% in the 3 mg kg−1 QD group (P = 0.009), and 75% vs. 61% in the 10 mg kg−1 QD group (P = 0.01). Patients with possible invasive mould disease based on EORTC/MSG 2008 criteria had improved survival rates compared with those treated for probable/proven invasive mould disease. As possible invasive mould disease probably reflects an early-stage of disease, a better outcome might be expected when treatment with liposomal amphotericin B is started preemptively. “
“Hearing is one of the major senses in whales and dolphins (cetaceans). This is the first report of severe mycotic otitis media in a cetacean, a juvenile female harbour porpoise (Phocoena phocoena) from British waters that stranded alive. Gross examinations were followed by histological and microbiological investigations of the auditory apparatus.

It should be noted, that TCR-mediated activation of CD8+ T cells alone in the absence of exogenous cytokines is sufficient to upregulate T-bet expression, at least to a certain extent (Fig. 5C and 4), but only sustained high-level expression of T-bet seems to be instructive for SLEC differentiation 4. BMS-777607 cell line In our in vivo experimental setup, it is also conceivable that low levels of IL-12 induced upon LCMV8.7 and VVG2 co-infection were contributing to the upregulation of T-bet in IFNAR−/−

P14 cells. Nevertheless, the extent of T-bet upregulation was not sufficient to drive the differentiation of IFNAR-deficient CD8+ T cells into SLECs which is in agreement with the demonstration that only high levels of T-bet expression favored SLEC differentiation upon transduction of T-bet−/− CD8+ T cells with a retroviral construct allowing for graded amounts of T-bet expression 4. In line with our observation that type-I IFN signaling can act as an instructive signal for SLEC differentiation, it was recently reported by Mescher and colleagues that type-I IFN can induce the upregulation

of certain effector molecules as well as the transcription factor T-bet in activated CD8+ T cells in vitro 9. As many in vitro differentiation studies use large amounts of cytokines which might not reflect the in vivo situation, it is important to consolidate such in vitro findings by in vivo data. Our results identifying direct type-I IFN signaling on CD8+ T cells https://www.selleckchem.com/products/Everolimus(RAD001).html as a differentiation factor of

SLECs, clearly support these in vitro data. Moreover, our results are in accordance with the previous in vivo data in the context of T-cell-mediated tumor control, where it was shown that supplementation of IFN-α to a peptide vaccination led to increased tumor Reverse transcriptase infiltration by effector CD8+ T cells and preferentially promoted the differentiation of CD8+ T cells with an effector memory like phenotype 14. In line with these results, we found that IFNAR−/− P14 cells were undetectable in peripheral tissue 45 days after infection as opposed to WT P14 cells which were found at high numbers in the liver of infected mice, indicating that type-I IFN is necessary for the formation of effector memory cells. This further suggests that type-I IFN is not only necessary for the short-term differentiation of SLECs but also plays a role in the long-term formation of effector memory cells. Although, qualitatively equivalent memory cells with respect to their recall proliferation potential formed the absence of type-I IFN signaling, suggestive of unaltered central memory CD8+ T-cell differentiation, there is a significant difference in the overall quantity of memory cells formed in the absence of type-I IFN signaling. Besides IL-12 and type-I IFN, IL-2 was found to act as a differentiation factor for CD8+ T cells 15, 16, 34, 35.

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, selleck compound 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% Selleckchem Copanlisib 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 4��8C (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.

[62-65] Our results suggest that RBV enhances the TAA-specific cellular immune response in association with down-modulation of Treg-cell activity. As previously reported for CPA,[66] this hypothesis may contribute to preventing the progression

to hepatocellular carcinoma in patients with HCV infection who were successfully treated with IFN plus RBV. To confirm this hypothesis, long-term observation of patients receiving pegylated IFN plus RBV therapy will be needed. In addition, it must be determined whether continuous Cobimetinib mouse administration of RBV after the elimination of HCV can contribute to the prevention of hepatocellular carcinoma. In this report, we demonstrated the ability of RBV to inhibit the differentiation of naive CD4+ T cells into CD25+ FOXP3+ Tregadapt cells through the inhibition of Treg1-type regulatory cells. Although the mechanism of action by which RBV regulates Treg cells is not fully understood, we expect that these findings will contribute to establishing a new approach

for regulating immune responses in patients with various diseases caused by immunological impairment. We are grateful to Dr Taku Tsukui, Division of Gastroenterology, Department of Medicine, Nippon Medical School, Tokyo, Japan, for critical reading of this manuscript and helpful suggestions. The authors declare that there is no conflict of interest. “
“Aeromonas have been isolated from a wide variety of aquatic environments.

However the number of Aeromonas in sea water is extremely small compared to that in fresh water. In in vitro culture, Aeromonas can grow in mediums containing Protein Tyrosine Kinase inhibitor NaCl at a concentration of 3.0%, this concentration corresponding http://www.selleck.co.jp/products/MG132.html to that of sea water. It is unclear why the number of Aeromonas is low in sea water. Exoproteins of bacteria are thought to be important for bacterial growth and survival in the environment. Previously, the present authors have shown that mediums containing 3.0% NaCl suppress production of two proteases, serine protease and metalloprotease. In this experiment, other exoproteins whose production is influenced by the amount of NaCl in the medium were analyzed. A protein whose production is repressed in medium containing 3.0% NaCl was found and purified. Biological assay of the purified protein showed that it degrades tributyrin and hydrolyzes para-nitrophenyl-fatty acylesters. These results show that the protein is a lipase. Subsequently, the nucleotide sequence of the gene encoding the lipase was determined and the amount of mRNA of the lipase gene in the cells measured. It was found that transcription of the gene is not inhibited by NaCl in the medium. This result indicates that the lipase might be synthesized, but the folding process to become an active structure does not progress smoothly in a medium containing 3.0% NaCl. Motile Aeromonas spp. (A. sobria, A. hydrophila, and A.

pneumoniae. The basal levels of cytokines and

the ones induced by the oral and nasal administration of the probiotic before immunization with recombinant strains (day 0) were determined. With regard to the IL-2 and IFN-γ Th1-type cytokines (Fig. 3a, b), the mice that received L. casei by the oral and nasal routes before administration of the vaccine (day 0) showed a significant increase in IFN-γ. Oral administration of Lc induced greater production of IL-2 compared to the control that received PBS. On days 28 and 42 there was a significant increase in GDC-0068 IL-2 and IFN-γ in BAL in all the groups treated compared to the control. LL + Lc (O) and D-LL + Lc (O) induced the highest level of IL-2, which would indicate that the probiotic influenced the increase in this cytokine compared to administration of LL [on day 42, LL versus D-LL + Lc (O): P < 0·001, LL versus LL + Lc (O): P < 0·01) and D-LL (D-LL + Lc (O) versus D-LL: P < 0·01, LL + Lc (O) versus D-LL: P < 0·001]. The concentration of IFN-γ in BAL reached highest levels in the group that received LL + Lc (O), followed by D-LL + Lc (N), with significant differences between them (LL + Lc versus find more D-LL + Lc (N): P < 0·01). With regard to the induction of the Th2-type cytokine IL-4, oral and nasal administration of Lc before immunization

with recombinant vaccine (day 0) induced a significant increase in IL-4 in BAL compared to

the control (Fig. 4a). Two weeks after the second (day 28) and third immunizations (day 42) with the recombinant strain, there was a significant increase in IL-4 in all experimental groups compared to the control (day 0). On days 28 and 42, the live and the inactivated vaccine associated with the probiotic strain administered by the oral and nasal routes induced high IL-4 levels in BAL compared MRIP to both the LL group [day 42, LL versus LL + Lc (O): P < 0·05) and the D-LL group (D-LL + Lc (O) versus D-LL: P < 0·01, D-LL versus D-LL + Lc (N): P < 0·01]. However, it should be noted that the highest levels of this cytokine, which is a marker of the stimulation of Th2 cells, was obtained with the nasal administration of the probiotic strain associated with the inactivated recombinant strain (P < 0·01). The regulatory cytokine IL-10 (Fig. 4b) showed variable behaviour depending upon the experimental group studied. The oral and nasal administrations of Lc induced high IL-10 concentrations compared to the control; however, the association of Lc (administered nasally) with D-LL (D-LL + Lc) induced a similar concentration to the control group on day 28. The highest IL-10 levels were reached 2 weeks after the second immunization (day 28) in the group that received D-LL (P < 0·001) compared to the control.

Commercial IVIG preparations contain multiple anti-idiotypic antibodies, such as anti-factor VIII antibodies [10], anti-DNA autoantibodies [11–13], anti-intrinsic factor antibodies [13], anti-thyroglobulin (Tg) autoantibodies [13], anti-neutrophil cytoplasmic antibodies [14], anti-microsomal antibodies [15], anti-neuroblastoma antibodies

[16], anti-phospholipid antibodies [17], anti-platelet antibodies [18], anti-Sm idiotype (ID-434) [19] and anti-GM1 antibody [20]. Therefore, in the last decade, IVIG has been used increasingly as an immunomodulatory agent in the treatment of autoimmune and systemic inflammatory diseases, including systemic lupus erythematosus, dermatomyositis and polymyositis, multiple sclerosis, myasthenia gravis, Guillain–Barré syndrome and anti-phospholipid syndrome [21,22]. Anti-idiotypic antibodies are effective in the treatment or prevention of disease manifestations because they inhibit the binding selleck chemicals llc of the pathogenic autoantibodies to their corresponding antigen, as shown both in vitro[12,13,23,24] and in vivo[17,19,25]. An in vitro study of systemic lupus erythematosus suggested that the value of anti-idiotypic antibodies may also be attributable to their

inhibitory effect on the spontaneous secretion of anti-desmoglein by peripheral B lymphocytes [26]. In addition, IVIG click here may act via the idiotypic network, causing soluble circulating immune complexes to aggregate and become insoluble and, consequently, removable by the reticuloendothelial system. Our previous study demonstrated the efficacy of IVIG in the prevention of blister formation in an experimental model of PV CYTH4 [27]. Recently, our positive findings were confirmed in a large double-blind placebo-controlled clinical trial [28]. The amount of specific anti-idiotypes in commercial IVIG preparations

is extremely low. Therefore, we speculated that the use of isolated anti-idiotypes against pathogenic autoantibodies could yield even better results with a fraction of the amount of IgG, with a lower rate of adverse reactions. To test this theory, we developed a modulated anti-idiotypic preparation using concentrated specific natural polyclonal anti-desmoglein anti-idiotypic antibodies from commercial IVIG. The aim of the present study was to evaluate the effect of treatment with IVIG affinity-purified anti-desmoglein anti-idiotypic antibodies on the immunological and clinical findings in a mouse model of PV. Desmogleins 1 and 3 single-chain variable fragment (scFv) was produced in the Top10F’ strain of Escherichia coli (Invitrogen, Carlsbad, CA, USA) and purified by nickel chelation affinity chromatography, as described previously [29]. Rabbit anti-desmogleins 1 and 3 were derived from rabbits immunized with anti-desmogleins 1 and 3 scFv and used as a source of anti-idiotypic antibodies.

4 and BCG were transported to Lamp+-compartments. BCG and TB10.4 however, were directed to different types of Lamp+-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different recognition of the same protein. The size, shape and nature of a synthetic recombinant vaccine and its target pathogen differ SB431542 ic50 significantly.

For instance, bacteria are typically in the range of 0.5–10 μm in diameter, which exceed the size of most viruses by 10 to 100-fold, and protein based adjuvanted vaccines are even smaller. In addition, compared with vaccines based on recombinant proteins and an adjuvant, pathogens are often taken up by different mechanisms BKM120 cell line by the cells of the immune system 1. The different uptake mechanisms could lead to different intracellular processing of Ag, giving rise to different epitopes 1. Furthermore, live pathogens express a wide range of specific lipids and proteins that bind

a variety of pattern-recognition receptors on phagocytes and induce signaling through these receptors, whereas recent evidence suggests subunit vaccines more specifically tend to target DC through activation of toll-like receptors 2. These differences are likely to lead to different responses with regard to the priming of the early immune response 3. For instance, the main host cell of the intracellular pathogen Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis in humans, is thought to be macrophages 4; however, although mycobacteria are mainly taken up by macrophages, mycobacteria

can infect a wide range of cells including neutrophils, epithelial cells and other cell types 5, 6. On the other hand, viral vaccine vectors have been shown to be ingested largely by immature DC 1, and soluble Ag formulated in cationic adjuvants such as CAF01 or IC31 are also believed to target DC 7, 8. Different types of APC have different mechanisms of Ag uptake, different pH levels in lysosomal compartments, express different protein VAV2 degrading enzymes and differ in their ability to process and cross-present Ag to MHC class I molecules 9. Even within the same type of APC, Ag uptake and intracellular transport may vary depending on the size and nature of the Ag/pathogen 1, 9. In addition, transport to different intracellular compartments can lead to processing of different epitopes 10. Thus, it is likely that different pathogens and vaccine vectors could result in different Ag processing. In the field of tuberculosis vaccine research, there has been considerable focus on identifying infection-driven as well as vaccine-induced epitopes in vaccine candidate Ag 11–15. Less research has focused on comparing whether the epitopes induced by immunization in fact differ from those recognized following infection with M.tb.