In DC-based immunotherapy, it is occasionally difficult to obtain a sufficient number of quality-guaranteed DC for some patient groups, such as: (1) paediatric cancer patients, who are too

small to receive leukapheresis for DC preparation [20], (2) cancer patients with pancytopaenia owing to cachexia or basal disease-related factors such as liver cirrhosis or (3) patients with haematological malignancy, in whom peripheral blood may be contaminated with a large number of viable malignant cells. In such patients, allogeneic DC may be an alternative source. It has been suggested that the host alloresponse to the injected DC may actually facilitate the antitumour response www.selleckchem.com/products/VX-770.html and that their alloantigens may work as helper antigens [21]. However, this theory is controversial [22, 23]. Moreover, click here some preclinical studies using murine s.c. tumour models have shown that s.c. immunization using fully allogeneic DC failed to induce antitumour effects [14, 24]; thus, the use of allogeneic DC in DC-based immunotherapy may be limited. When allogeneic DC are used for cancer immunotherapy, three important factors must be considered. First,

the major histocompatibility complex (MHC) incompatibility of the DC used may be the most important factor for priming the MHC-restricted TAA-specific CD8+ T cells [25, 26] because during T-cell development, the host T cells acquire MHC restriction because of positive selection [27] by somatic cells (cortical thymic epithelial cells (cTECs), which are the crucial APC for expressing the MHC), rather than

haematopoietic cells [27]. Second, the survival of injected allogeneic DC may be shortened by T-cell-mediated rejection, and this may have an effect on the resulting antitumour response because DC survival is an important factor in priming antigen-specific T-cell responses. Third, it is not known whether host-derived pAPC can function in an antitumour capacity in DC-based immunotherapy, especially via the i.t. injection route. Until Parvulin now, no experimental model has been developed that assesses these factors individually, and it is unclear which of the factors, and to what degree, will affect the antitumour responses of allogeneic DC. It is also unclear which injection route is most preferable when using allogeneic DC. Here, we aimed at evaluating the availability of allogeneic DC for DC-based immunotherapy and to elucidate the mechanism for the antitumour effect, focusing on the three important factors related to allogeneic DC. We demonstrate that s.c. immunization using semi- or fully allogeneic DC pulsed with tumour lysate has a limited antitumour effect and does not induce a significant number of IFN-γ-producing tumour-specific CD8+ T cells. When semi-allogeneic DC were injected via an i.t. injection route, we observed the induction of an efficient antitumour response and a significant tumour-specific CD8+ T-cell response.

Recently, we found that reduced expression of Fli-1 protein had a profound effect on disease development in the NZM2410 mice that are a strain derived by intercrossing NZW × NZB F1 mice. Fli-1+/− NZM2410 mice, like Fli-1+/− MRL/lpr mice, had significantly lower serum

autoantibody titres and decreased proteiuniria compared to WT NZM2410 mice. Autophagy inhibitors high throughput screening Fli-1+/− NZM2410 mice survived significantly longer compared to WT NZM2410 mice (unpublished data). However, Green et al.[25] demonstrated recently that non-haematopoietic factors also contribute to lupus disease development in the α-mannosidase II-deficient mice model. We believe that our data also support an effect of non-haematopoeitic cells on MRL/lpr mice disease development based on the decreased disease in the Fli-1+/− MRL/lpr mice receiving BM from WT MRL/lpr mice. Using mice with specific cell Fli-1 disruption will provide further insight into how Fli-1 affects lupus disease development. We are now generating conditional Fli-1 knock-out MRL/lpr mice for future study. In summary, our data demonstrate that the expression of Fli-1

in BM derived haematopoietic cells has a significant effect on autoimmune disease development in MRL/lpr mice and that decreased expression of Fli-1 in non-haematopoietic cell lineages also probably contributes to the improvement of autoimmune disease development in MRL/lpr mice, These data also indicate that the expression of a single gene in different cell types can have separate but synergistic effects on disease development. This study Thiamet G was supported by National Institutes CHIR-99021 of Health grants (AR054546 to X. K. Z.) and the Medical Research Service, Department of Veterans Affairs (to X. Z. and G. G.). None. “
“Sjögren’s syndrome (SS) is an autoimmune inflammatory disease that primarily affects the lacrimal and salivary glands causing dry eyes and mouth. Antibodies to Ro60 are frequently observed in patients with SS; however, the role of these antibodies in SS initiation and progression remains

unclear. The sequence Ro60 273-289 (Ro274) is a known B cell epitope of Ro60and antibodies to this epitope have been observed in a subset of SS patients and in animals immunized with Ro60 protein. Animals immunized with Ro274 linear peptide develop a Sjögren’s-like illness. We hypothesized that passive transfer of anti-Ro274-specific IgG would induce a Sjögren’s-like phenotype. To evaluate this hypothesis, we adoptively transferred affinity-purified Ro274 antibodies into naïve BALB/c animals then evaluated salivary gland histology, function and IgG localization four days post-transfer. At this timepoint, there was no demonstrable mononuclear cell infiltration and salivary glands were histologically normal, but we observed a functional deficit in stimulated salivary flow of animals receiving Ro274 antibodies compared to animals receiving control IgG.

However, Selleckchem Crenolanib further studies are needed before recommending the use of these drugs safely in clinical situations. “
“There is scarcity of data regarding significance of candiduria in patients with haematologic malignancies and its association with invasive candidiasis. To that end, we retrospectively evaluated all hospitalised, non-intensive care unit patients with haematologic malignancies and candiduria during a 10-year period (2001–2011). To decrease the possibility of bladder colonisation and sample contamination, we excluded all patients with candiduria who had urinary catheters and those with concomitant bacteriuria. Twenty-four such patients (21 females) were identified,

with median age at diagnosis 62 years

(range, 20–82 years). Acute leukaemia was the most common underlying disease (54%); 62% of these cases were not in remission. Twenty-nine percent of the patients had diabetes mellitus and 25% were neutropenic. The most common isolated Candida species was Candida glabrata (37%), followed by C. albicans (29%). Only 8% of them had urinary tract infection symptoms. However, 88% received systemic antifungals. Candidemia and crude mortality rates at 4 weeks were low (4% and 12% respectively). Isolated candiduria in patients with haematologic malignancies Gefitinib has risk factors similar to those in other hospitalised patients, and it does not seem to be a strong predictor of subsequent invasive candidiasis. “
“Two Candida albicans isolates were collected from a HIV-positive patient with recurrent oropharyngeal candidosis (OPC). One isolate was taken during the first episode of oral candidosis [fluconazole susceptible (FLU-S), minimal inhibitory concentration (MIC) = 0.25 mg l−1] and the second after the patient developed refractory OPC and resistance to fluconazole (FLU-R, MIC = 64 mg l−1). Both isolates were clonally identical. Different in vitro studies were carried out to assess putative virulence factors of both isolates. Gene expressions of efflux pumps and CSH1 were determined as well as adherence to human epithelial cells, determination of proteinase secretion and biofilm

formation activity. Virulence was studied using a disseminated mouse model. All mice challenged with the FLU-S isolate survived the experiment when Sinomenine FLU was given. However, when FLU was absent, the mortality of the FLU-S isolate was higher than that of the FLU-R isolate with no mice surviving the experiment. In vitro studies showed pronounced growth rates of the FLU-S isolate and a more intense biofilm-building activity compared with the FLU-R isolate. The FLU-R isolate highly up-regulated MDR1 and CSH1. This isolate also adhered stronger to the epithelial cell line. The results showed that FLU-S and FLU-R isolates exhibit different virulence factors, which enable the survival of both isolates in adapted environments.

The only other study to examine Tregs within canine tumours found similar results to

the many other GSK1120212 concentration studies of human tumours and experimental cancer models. They reported that the percentage of FoxP3+ CD4+ cells in dogs with malignant melanoma was significantly increased in the blood compared with healthy control dogs, and the percentage of FoxP3+ CD4+ cells within tumours compared to blood was also significantly increased (31). Therefore, this study clearly demonstrates that the developing dogma that FoxP3+ T cells are highly prevalent in tumour-associated inflammation is not universally true and emphasizes that malignant transformation can still occur in the absence of immunosuppressive FoxP3+ T cells. It is in agreement with the canine literature find more on sarcoma (16), especially osteosarcoma (32). Interestingly, in humans with Ewing’s sarcoma, there was also no infiltration of FoxP3+ cells into the tumours, whereas in patients with metastases, the number of FoxP3+ cells only increased in the bone marrow (33). The fact that a large number of positive cells were observed in a few cases, as well as in lymph nodes, but not in the iso- or tissue controls,

excludes technical error. Moreover, all samples were fixed by the same method (formalin-fixed and paraffin-embedded), and the nine positive controls (lymph nodes) originate from nine of the study cases. Therefore, it seems feasible that there is a real difference in the immune response to sarcomas (especially in dogs), compared to other tumours, especially melanomas. The possible role of Tregs in the pathogenesis of spirocercosis-induced sarcoma is especially intriguing, because of the well-documented role of Tregs in helminth infection. In chronic helminth infection (and spirocercosis-induced inflammation is, indeed, chronic) Tregs reduce the intensity of the infection (8). There

is evidence that the increased Tregs response facilitates long-lasting chronic Protein kinase N1 inflammation that reduces auto-immunity and allergy in infected subjects (34). This notion is part of the proposed mechanism of what is known as the ‘hygiene hypothesis’ that describes the association between of helminth infection and low incidence of autoimmunity (35). The Tregs-induced increased ‘self-tolerance’ may reduce anti-tumour immunity, and this could potentially be the link between spirocercosis and tumour formation. It appears, however, that although FoxP3+ cells were circulating in lymphatics around S. lupi nodules, ‘homing’ into the nodules did not take place. The low number of FoxP3+ cells does not entirely preclude their potential role in local or systemic immune inhibition in spirocercosis, but functional assays are required.

We performed 5′ RACE using degenerate primers based on a conserved C domain amino acid sequence to isolate putative dromedary TCRG chain cDNA clones. A total of 20 cDNA clones were selected, and two groups of clones were identified which shared selleck screening library almost identical C region sequences (nucleotide identity of 89%), which were respectively named TCRGC2 and TCRGC1 (Supporting Information Table 1). A BLAST search showed that the clones shared significant identity with known TCR γ chains, the best match being with the TCR γ chain of artiodactyls (ruminants and pig). The complete

sequences of the C regions were assembled using cDNA clones from 3′ RACE. A comparison of the deduced amino acid sequence of the two assembled

C regions with sheep and human sequences, as well as the boundaries of their conserved extracellular domain (C-DOMAIN), connecting (CO), transmembrane (TM), and cytoplasmatic (CY) domains, is shown in Figure 1A. Considering the exon organization of the ovine and human C regions, we inferred that both the dromedary C regions keep a connecting region encoded by three different exons, as is observed in the sheep TCRGC2, CT99021 price TCRGC4, and TCRGC6 genes [15] and in the polymorphic human TCRGC2 gene [2, 16]. The two cysteines involved in the intrachain disulfide bond (positions 23 and 104 according to the IMGT unique numbering [17]) and those involved in the interchain disulfide bond are conserved, as well as the lysine (Lys K) amino acid in the TM region required for interaction with CD3γ. Furthermore two TCRGV genes and two distinct TCRGJ genes were identified within the variable domain of the cDNA clones. The TCRGV genes were classified in two distinct TCRGV1 and TCRGV2 subgroups. Sequence comparison with the available database entries indicates a high level of similarity Phosphatidylinositol diacylglycerol-lyase with the ovine TCRGV6-1 and pig TCRGV5-1 functional genes (Fig. 1B), whereas its most strictly related counterpart in human (the TCRGVA gene) is a pseudogene. Similarly, the TCRGV1 gene subgroup has the highest level of similarity with TCRGV genes of artiodactyls (ovine TCRGV9-1 and

pig TCRGV6-1) (Fig. 1B). The sequence analysis of the isolated cDNA clones suggests the presence of two TCRG cassettes. Dromedary lung DNA was purified to perform sequencing of the germline TCRG locus. Both genomic PCR and Genome Walker DNA walking strategies were used. The sequence was assembled from ten PCR products and three chomosome walking fragments and in most cases was derived from at least two independent products. A gap in the genomic sequence exists between TCRGJ1-1 and TCRGC1. However, we identified a partially assembled lama (Lama pacos) genomic scaffold (acc. ABRR01332756.1) similar to dromedary TCRG1 cassette (see Materials and Methods). We found out that another TCRGJ gene (TCRGJ1-2) is present downstream of TCRGJ1-1 in the lama genome.

101 It is known that heavy proteinuria develops with pathological changes of mesangial apoptosis and recruitment of neutrophils and monocytes into the mesangium, followed by release of chemoattractant, pro-inflammatory cytokines and subsequent mesangial hyperproliferation and matrix expansion. Blocking this process is associated with significant reductions in urinary protein

excretion. Panichi’s group were able to ameliorate mesangial inflammation with the administration of 1,25-OHD, which reduced inflammatory check details cell recruitment and cytokine production (measured as urinary IL-6), together with associated decreases in mesangial cell proliferation.104 Similar results were obtained by Makibayashi’s lab using the same model but with the VDR activating 1,25-OHD analogue 22-oxa-calcitriol (OCT).105 In addition to the cellular changes reproduced, this group also demonstrated a reduction in mesangial matrix, selleck chemicals llc with diminished expression of mRNA and staining for type I and IV collagen, and α-smooth muscle actin (α-SMA). This effect may be mediated through modulation of transforming growth factor-β (TGF-β) which is known to modulate mesangial cell proliferation106 and in Makibayashi’s study diseased glomeruli showed strong staining for TGF-β1 with upregulated mRNA expression which was greatly reduced Celecoxib in the treatment

group.105 This effect on TGF-β had been seen in an earlier study by Schwarz et al. who used subtotally nephrectomized rats as a model of glomerular remodelling and sclerosis.107 In 1,25-OHD-treated diseased rats, the group effectively reduced glomerulosclerosis and mean volume of individual glomeruli – a marker of hypercellularity, matrix expansion and proliferation. This was associated with diminished in situ hybridization for cellular TGF-β, and most importantly a significant reduction in albuminuria.107 The clinical translation of this work has recently been published by the VITAL investigators.108 In this well-designed placebo-controlled, double-blind trial,

281 patients with diabetic nephropathy were randomized to placebo, 1 µg/day or 2 µg/day paricalcitol, in addition to standard renin-angiotensin blockade for 6 months. There was a significant reduction in urinary albumin excretion in the paricalcitol groups compared with placebo which demonstrated a dose–response relationship and was most evident between the placebo and 2 µg/day groups (−3% (95% CI: −16 to 13) vs−20% (95% CI: −30 to −8), P = 0.053). This was accompanied by a substantial, early sustained reduction in eGFR (−3 to −5 mL/min/1.73 m2, P = 0.055) and systolic blood pressure (−3 to −9 mmHg, P = 0.033), implying that paricalcitol may improve albuminuria via suppression of the renin-angiotensin system.

6c). The present study provides evidence for a role of the CCR3/Eotaxin pathway in local proliferation and mobilization of CD34+ cells in the airways after allergen exposure. We have determined that CD34+ CCR3+ cells increase in BM, blood and airways after allergen exposure, and further demonstrated that allergen-induced newly produced eosinophil-lineage-committed (CD34+ CCR3+ BrdU+) lung cells have the capacity to proliferate in situ after allergen exposure. Significantly, IL-5 and eotaxin-2 each alone Smoothened Agonist solubility dmso stimulated

in vitro CFUs of lung CD34+ cells but not BM CD34+ cells. Moreover, delivery of eotaxin-2 to the airways of IL-5 transgenic mice resulted in a substantial increase of CD34+ cells in BAL and in vitro transmigration assays show that BM and blood CD34+ CCR3+ cells migrate in response to eotaxin-2. These data, together with our observations showing that systemic treatment with a depleting anti-CCR3 antibody abolished

both CD34+ and Sca-1+ cells in airways to levels similar to control animals, suggest a role of this chemokine receptor in lung progenitor cells. The present study showed that allergen-sensitized and allergen-exposed animals displayed a significant increase in CD34+ CCR3+ cells (relative to allergen-sensitized but saline-exposed animals) in not only the BM, but also in blood and airways. We further demonstrate that a proportion of the CD34+ CCR3+ cells in the airways stain positively for Sca-1, which confirms that some of these cells are likely to be haematopoietic stem cells. That is, Sca-1 PD98059 is considered to be a stem cell marker, and has recently been shown to be involved in regulating the repopulation ability of haematopoietic stem cells in mice.28,29 Previously it had been shown

that both immature and mature BM eosinophils express CCR3 and that the expression is higher in BM from patients with atopic asthma compared with controls, suggesting that there is an increased pool of CCR3+ immature and mature eosinophils available for rapid mobilization.14,30,31 In addition, the expression of CCR3 has been shown to be up-regulated during maturation of CD34+ cells to circulating eosinophils, suggesting a role in the trafficking of metamyelocytes to inflamed tissue.31 Furthermore, an increase Cetuximab supplier in CD34+ cells in sputum has been reported in atopic asthmatic patients as well as in nasal polyp tissue.32 The increase of CD34+ cells in the nasal mucosa of patients during a pollen season, suggests that progenitors are recruited into the local airway tissue by allergen-dependent mechanisms; here they may differentiate into more mature cells within the site of allergic inflammation (i.e. in situ haematopoiesis).13,22,33–35 These parallel phenomena in allergic mice and asthmatics imply that the mouse model has relevance to the human disease in relation to eosinophil maturation and trafficking.

FoxO family members are responsible for the response to stress and growth factors [47], but have also been implicated in immune tolerance [48]. Consistent with these findings, in our monocyte/T-cell co-culture experiments IRAK4-silenced monocytes suppress the activation of allogenic CD8+ and CD4+ T cells (Fig. 7A). Blocking of IL-10 in the co-culture or addition of rhIL-10 (mimicking the IRAK4-deficient cytokine profile) demonstrated that this effect is exerted by IL-10 (Fig. 7B and C). To date, little is

known about the early events in TLR signaling that favor the formation Selleck Caspase inhibitor of monocytes with suppressive function. Nevertheless, our data highlight a tolerogenic function of IRAK4 and the PKB/Akt pathway in human monocytes. Altogether, this prompted us to suggest that IRAK4 acts as differential modulator of TLR-activated cytokine production, consequently representing

a switch between pro- and anti-inflammation. Blood draw and use of human leukocytes upon informed consent of healthy donors were approved by the ethics committee of the University of Heidelberg, Germany (approval number 157/2006). Peripheral this website blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density gradient centrifugation. Human monocytes were isolated by positive selection with anti-CD14 microbeads (Miltenyi Biotech, Bergisch-Gladbach, Germany). The purities obtained were ≥ 95%. T cells were isolated using anti-CD8 or anti-CD4 microbeads (Miltenyi Biotech). The purity was ≥96%. Isolated cells were resuspended in RPMI 1640 (Invitrogen, Karlsruhe, Germany) supplemented with 100 IU/mL of penicillin, 100 μg/mL streptomycin, 1% L-Glutamine, and 1% HEPES buffer (all from Sigma-Aldrich, Munich, Germany) containing 5% heat-inactivated autologous human serum or 10% FCS (Invitrogen, Karlsruhe, Germany). If not stated otherwise, monocytes and T cells were used at 1×106 per mL. Stimulatory reagents were used at the following concentrations, unless indicated otherwise: highly purified LPS from Salmonella (10 ng/mL; gift from U. Zaehringer, Research Center Borstel, Borstel, Germany) and Pam3CSK4 (200 ng/mL; EMC Microcollections, Tuebingen, Germany).

The IL-10 neutralizing mAb and the goat Thymidylate synthase IgG isotype control (R&D Systems; McKinley Place, MN, USA) were dissolved in PBS and used at 10 μg/mL. Recombinant human IL-10 (Peprotech, Hamburg, Germany) was dissolved in PBS and titrated from 1 to 10 ng/mL. The inhibitors rapamycin (10 ng/mL), wortmannin (1 μM), FK506 (10 nM), AG490 (10 μM), SB415286 (10 μM), U0126 (10 μM) (all from Enzo Life Science, Loerrach, Germany), SB203580 (10 μM), JNK inhibitor II (10μM) Bay11–7082 (Bay11; 50μM) (all Calbiochem, Darmstadt, Germany), Akt inhibitor VIII (50 μM; Calbiotech, San Diego, CA, USA) and IRAK1/4 small molecule inhibitor [49] (50 μM; Sigma Aldrich, Steinheim, Germany) were dissolved in DMSO (Sigma-Aldrich). Cyclosporine A (CsA) (0.5 μM; Enzo Life Science) was dissolved in ethanol. S.

At 7

days after implantation, cells double-positive for GFP and myoglobin and cells double-positive for GFP and SMA are present within the wound region as isolated cells that are not in physical contact with each other. In contrast, by 14 days the GFP and myoglobin double-positive cells are in contact with each other and with non-GFP expressing striated cells derived from uninjured surrounding tissues. Similarly, the GFP and SMA double-positive cells also contact each other and non-GFP expressing smooth muscle cells. The association of these cells forms higher order layered muscle structures within the urethral sphincters. Fulvestrant Furthermore, within the developing musculature, there are blood vessel walls containing smooth muscle cells that are double-positive for GFP and SMA. These results suggest that the striated muscle

and smooth muscle cells derived from implanted bone marrow-derived cells may advance the reconstruction of muscle tissues and vascular components to support them. At 7 days after cell implantation, a few of the GFP-labeled implanted cells are simultaneously positive for Pax7 (Fig. 4e), suggesting that they have myoblast properties. In the development process to mature muscle, Pax7 acts as transcription factor, and satellite cells and myoblasts both express Pax7, but mature muscle cells do not. Currently DMXAA clinical trial we cannot determine if the cells expressing both GFP and Pax7 are presumptive satellite cells or myoblasts. Nevertheless, the implanted cells clearly follow a development process that leads to the differentiation of striated or smooth muscle cells. The number of the cells expressing both GFP and Pax7 on day 14 is distinctly higher than on day

7 (Fig. 4f). Myoblasts properly differentiate into striated or smooth muscle cells according to surrounding environment.2 The greater number of Pax7 cells on day 14 compared to day 7 suggests that the formation rate of differentiated muscle cells may have decreased or even stopped. This suggests that the process of new striated and smooth muscle cell differentiation Resminostat is under some type of intrinsic regulation. Understanding the controls for differentiation of the implanted cells is very important for further development of regenerative medicine. While the details of this regulation are currently unknown, it is clear that the presence of the myoblasts in the regenerated region may have important long-term significance. In the event that the newly differentiated striated and/or smooth muscle tissues and structures spontaneously regress or are lost for other reasons, the presence of the myoblasts could ensure the replacement of the lost cells. Thus, the effects of treatments may be maintained for long periods of time. To develop regenerative medicine, we must investigate and provide various cell sources that are best suited to the health conditions and lifestyles of our patients.

e. inflammatory interstitial pneumonitis,

de novo glomerulonephritis and systemic inflammatory response syndrome).[34] Together with the described role of the phosphatidylinositol 3-kinase–mTOR pathway in limiting the production of pro-inflammatory cytokines after stimulation by TLR agonists or CD40 ligand,[34] the relevance of mTOR pathways in M2 survival and M1 polarization could explain the distinct inflammatory side-effects observed during RAPA treatment. In conclusion, we demonstrate that RAPA affects M2 survival and unbalances H 89 clinical trial to an M1-like inflammatory response both in vivo and in vitro. Consequently, our work proposes the mTOR pathway as a key regulator of macrophage polarization and offers a novel mechanistic insight in macrophage polarization. Due to the availability of mTOR inhibitors for clinical therapy, the effect on macrophage polarization may open the way for mTOR targeting and tailoring in M2-related human diseases. This work was supported by EU (HEALTH-F5-2009-241883-BetaCellTherapy), Juvenile Diabetes Research Foundation (JDRF Grant: 6-2006-1098, 31-2008-416, 4-2001-434, JT01Y01, 17-2011-601). The authors declare that they have no financial disclosures or competing interests. “
“Salivary host-defence peptides include defensins, histatins and cathelicidin. We have investigated the effects of these peptides on the microbial

composition of dental plaques. Salivary consortia, established within Rucaparib hydroxyapatite disc models, were exposed during development to physiological levels of human neutrophil proteins (HNP) 1 and 2; human β defensins (hβD) 1, 2 and 3; histatins (His) 5 and 8; and cathelicidin (LL37). Effects on aggregation and microbial composition were determined using fluorescence microscopy; and differential culture with PCR-DGGE, respectively. LIVE/DEAD microscopic analysis indicated

that HDPs decreased total bacterial viability, whilst β defensins, paired HNPs, His 5, His 8 and the HDPs combined inhibited bacterial aggregation. According to differential culture, all test HDPs (except His 5) significantly decreased the abundance of Gram-negative medroxyprogesterone anaerobes and lactobacilli (except HNP 2, hβD 1, paired HNPs and His 5). Combined HNPs and paired hβD 1 and 3 inhibited streptococci, whereas HNP 1, hβD 1, hβD 3, His 5 and LL37 increased streptococcal numbers. According to cluster analyses of DGGE profiles, HDP-exposed plaques were compositionally distinct from undosed controls. Thus, whilst HDPs reportedly exhibit variable potency against oral bacteria in endpoint susceptibly tests, exposure of nascent plaques can markedly influence bacterial viability, composition and microbial aggregation. Saliva contains a range of antimicrobial molecules of which over 45 have been characterized (reviewed by Gorr & Abdolhosseini (2011)).