Additive (AA versus AB versus BB) model was used for the tests of association by genotype and diplotype. Diplotype is defined as a specific combination of two haplotypes. The statistical analyses were performed using PLINK version 1.07 (http://pngu.mgh.harvard.edu/~purcell/plink).

Haploview 4.2 (http://www.broad.mit.edu/mpg/haploview/) was used with Gabriel’s rule to determine the haplotype and linkage equilibrium (LD) structure of the ALOX5AP gene. The SNP rs9506352 associated significantly with FEV1 when the Ansung data were examined separately or combined data AG-014699 in vivo [P = 0.009 and 0.006 (permuted P = 0.045 and 0.032), respectively]; FEV1 increased by 2.616 and 1.246 per the minor A allele was present, respectively. The SNP rs10162089 and rs3803277 were significantly associated with FEV1 in combined data (P = 0.027

and 0.011), FEV1 increased by 0.968 and 1.008 per the minor A and C allele was present, respectively. In contrast, FEV1/FVC did not associate significantly with any of the SNPs in the Ansan, Ansung, or total populations. Table 2 indicates the associations between the SNPs in the ALOX5AP and FEV1 or FEV1/FVC. Two LD blocks were identified among the 13 intronic SNPs in the ALOX5AP gene (Fig. 1). The haplotypes with frequencies below 5% were filtered out. Ten SNPs were included in the second LD block, which had a relatively high D’ (>0.9) and R2 value as well as containing two exons. Therefore, diplotypes with tagging PF-02341066 supplier SNPs were used for analysis. Each LD block had three and four haplotypes, respectively. Of these, the diplotype of haplotype AA in block 1 associated significantly with FEV1 (P = 0.023); FEV1 increased 0.997 per haplotype AA was existed. The diplotype

of haplotype TCAC in block 2 also associated significantly with FEV1 (P = 0.008 and permuted P = 0.044); FEV1 increased by 1.230 per haplotype TCAC was present. FEV1/FVC did not associate with any diplotypes. Table 3 indicates the associations between the diplotypes in the ALOX5AP and FEV1 or FEV1/FVC. The SNP rs9579648 was associated with FEV1 in Ansan data (P = 0.044); Isoconazole FEV1 decreased by 2.660 per the minor G allele was present. Except rs9579648, SNPs in ALOX5AP showed no significant interaction with smoking on both FEV1 and FEV1/FVC. (Data not shown). In the results of analysis for general population (8535 subjects), for one minor allele of rs10162089, FEV1 was 1.135 and 0.622 higher as compared to wild type carriers in Ansung and combined data (P = 0.023 and 0.041, respectively). The SNPs rs9506352 was associated with decreased FEV1 in Ansung and combined data (P = 0.020 and 0.019, respectively); FEV1 increased by 1.225 and 0.749 per the minor A allele was present. For one minor allele of rs3803277, FEV1 was 1.224 and 0.823 higher as compared to wild type carriers in Ansung and combined data (P = 0.007 and 0.003 (permuted P = 0.033 and 0.014), respectively).

A protein array screen selleck chemicals revealed a large fraction of these molecules to be chemotactic cytokines or chemokines.[32] The MSC-conditioned medium therapy resulted in a 90% reduction of apoptotic hepatocellular death and a threefold increment in the number of proliferating hepatocytes with improved animal survival.[33] However, it should be noted that the factors involved in immunosuppression exert their activity in a short-range fashion, making it difficult, if not impossible, to reproduce the same magnitude of activity by injecting MSC-conditioned media. Furthermore, as discussed

later, the inflammatory environment is particularly important in shaping the functional profile of MSC and appears to be crucial also for the therapeutic success. There are at least two reasons selleck compound accounting for the potency of MSC-mediated immunosuppression. One is the co-operation/synergism of the

various soluble factors identified and described in the previous section. The other aspect, which is gaining support, is that MSC can recruit other immunoregulatory networks. Early in vitro studies in both murine and human MSC have shown that the inhibitory effect is not dependent on CD4+ CD25+ regulatory T (Treg) cells, because removing Treg cells in culture did not prevent immunosuppression.[20, 34] However, it has subsequently been found that MSC can increase regulatory T cells when co-cultured with CD4+ cells in vitro.[35] Systemic administration of MSC has been observed to protect the airways from allergen-induced pathology by inducing CD4+ FoxP3+ Treg cells and modulated cell-mediated responses at a local and systemic level, decreasing IL-4 but increasing IL-10 in bronchial fluid and from allergen-stimulated splenocytes. Thiamine-diphosphate kinase In this experimental system the use of metronomic doses of cyclophosphamide, which reduce Treg-cell responses, reduced the beneficial

effect of MSC. Further evidence of Treg-cell activation has been achieved in solid organ transplantation whereby the administration of MSC was observed to favour the differentiation of donor-specific Treg cells.[36-40] In models of autoimmune diseases, MSC effectively prevent the bone and cartilage damage produced by collagen-induced arthritis and such an effect is associated with the in vivo induction of antigen-specific Treg cells.[41] Similarly, human MSC stimulate IL-10-producing T cells and FoxP3+ CD4+ CD25+ T cells, with the capacity to suppress collagen-specific T-cell responses.[42] Moreover, non-classical CD8+ Treg cells have been identified as a result of co-culture of peripheral blood mononuclear cells with MSC.[43] The activation of Treg cells may have negative implications in the therapeutic field because of the well-known facilitating effect on tumour escape from immunosurveillance.

The abluminal membrane and most attached caveolae were devoid of terbium labeling. learn more Dual axis tilting

generated tomograms with better resolution than those acquired from single axis tilting. Reconstructed tomograms revealed discreet, unattached vesicles both labeled with terbium (Figure 3 and Video S1a) and unlabeled (Figure 4 and Video S2). Thresholding and surface rendering of a labeled free vesicle clarified its relationship with other vesicular structures and surface membranes (Video S1b). Translation of a single orthoslice through the model verified the accuracy of the model representing terbium deposition and the vesicle interior (Video S1c). A similar tomographic series through an unlabeled vesicle showed it appearing and disappearing without any connection with

other vesicular compartments (Figure 4, Video S2) In another tilt series, a large membranous compartment was revealed to be connected to selleck kinase inhibitor both luminal and abluminal membranes (Figure 5). Only the luminal membrane of the compartment exhibited bound terbium indicating the absence of glycocalyx on the abluminal portion of the compartment (Video S3). This structure represents a large thoroughfare through the capillary wall not commonly seen in continuous capillaries. In several regions, vesicles labeled with terbium were attached to the abluminal membrane by a stoma (mouth) (Figure 6, Video S4) and presented the possibility of a transendothelial C-X-C chemokine receptor type 7 (CXCR-7) channel. In one instance, a single tomographic

slice indicated a transendothelial channel open to both luminal and abluminal surfaces (Figure 6A). A tomographic series acquired at one of these locations showed a labeled abluminal vesicle that appeared connected to the lumen of the capillary (Figure 7). Creating a model of this vesicular compartment interior by thresholding the terbium revealed a channel-like structure through the capillary wall (Video S5a). An animated journey through the channel was generated with Amira beginning at the abluminal stoma (mouth) of a caveola, a rotation of the camera perspective in mid-channel and backing out through the luminal side (Video S5b) The anatomical correlates of transport pathways across continuous capillary walls have long been a subject of vigorous debate [4,11,18,20,21,23]. Pappenheimer et al. [15] postulated the existence of a single system of small pores (3–5 nm radius) to account for microvascular permeability. Grotte [6] introduced the concept of an additional smaller population of large pores (15–25 nm radius) to account for the transport of larger solutes. These estimates were based on the transendothelial transport dynamics of a range of different-sized solutes. Recent estimates of the ratio of large pores to small pores in skeletal muscle capillaries are about 1/5000 [12].

The periodontal pathogens were detected from saliva samples with conventional PCR. Although saliva is practical to collect, for periodontal pathogen analysis, it is diluted compared to subgingival bacterial samples.

selleck chemical The detection rates of the pathogens by the PCR were also lower than those published by quantitative PCR [29]. Therefore, the sensitivity of the methods used may limit the findings in the present study. A limitation of our present study is that the population is quite small with relatively low statistical power for sub-grouping. In addition, we do not have information on clinical periodontal status with determinations of attachment level, probing pocket depth and bleeding on probing. A clinical examination was not performed at baseline owing MAPK Inhibitor Library cost to the serious cardiac condition of the subjects. Previously, however, radiographs have been shown to be useful in evaluating and assessing the severity of periodontitis in epidemiologic studies [16, 30, 31]. Especially, P. gingivalis antibody levels remained remarkably stable during the follow-up of 1 year. This may reflect the chronic nature of periodontitis, a result in line with previous studies [32–35]. As expected, patients harbouring

P. gingivalis in their saliva had higher serum antibody levels against the pathogen than patients negative for it. Aggregatibacter actinomycetemcomitans IgA and IgG antibody levels increased slightly in the follow-up with a

concomitant increase in the HSP60 antibody levels. Therefore, the positive correlation between A. actinomycetemcomitans and HSP60 antibody levels was seen in all time points. As a summary, in patients with ACS, neither the presence of periodontal pathogens in saliva nor the periodontal status related to the serum HSP60 antibody levels. The systemic exposure of A. actinomycetemcomitans, however, associated with HSP60 GPX6 antibody levels suggesting that this proatherogenic periodontal pathogen results in both specific and unspecific immune response. We thank Ms Tiina Karvonen and Ms Pirjo Nurmi for technical assistance. This study was supported by grants from the Academy of Finland (118391 to PJP) and the Sigrid Juselius Foundation (PJP). None declared. Juha Sinisalo, Markku S. Nieminen, and Ville Valtonen: designing of the study and collecting the patients; Susanna Paju, Pekka Saikku, Maija Leinonen, and Pirkko J. Pussinen: determinations of the antibody levels; Susanna Paju: periodontal diagnosis from the X-rays; Hatem Alfakry, and Pirkko J. Pussinen: statistical analysis and interpreting the results; Hatem Alfakry: drafting the manuscript; Hatem Alfakry, Susanna Paju, Juha Sinisalo, Markku S. Nieminen, Ville Valtonen, Pekka Saikku, Maija Leinonen, Pirkko J. Pussinen: critical review of the manuscript.

In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT

mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ+ and IL-17+ CD4+ T cells and reduced MK-8669 concentration IFN-γ and IL-17 production but with increased frequency of IL-5+ and IL-4+ CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis. “
“Interleukin-7 (IL-7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α-chain of the IL-7R is polymorphic with the existence of SNPs that give rise to non-synonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment-related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation

(HCT). Some studies have confirmed an association between SAHA HDAC supplier rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic significance of IL-7Rα SNP genotypes in 590-recipient/donor pairs that received HLA-matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The Tallele of rs6897932 was suggestive of an association with increased frequency

of relapse by univariate analysis (P = 0.017) and multivariate analysis (P = 0.015). In conclusion, this study provides further evidence of a role of the IL-7 pathway and IL-7Rα SNPs in HCT. Interleukin-7 Protirelin (IL-7) is essential for T cell development in the thymus [1] and maintenance of peripheral T cells [2]. IL-7 receptor (IL-7R) consists of the common gamma-chain (CD132) as well as an α-chain (CD127). The α-chain of the IL-7R is polymorphic with the existence of four non-synonymous single nucleotide polymorphisms (SNPs) in the exons; rs1494558 (+510C/T in exon 2), rs1494555 (+1237A/G in exon 4), rs6897932 (+2087T/C in exon 6) and rs3194051 (+3101A/G in exon 8) that all give rise to amino acid substitutions [3, 4]. The α-chain is also used by the receptor of thymic stromal lymphopoietin (TSLP), a cytokine with complex effects on cytokine profiles, including stimulation of TNF production by dendritic cells (DC) and the induction of Th2 cytokines [3, 5, 6].

β-hexosaminidase is a generally accepted marker for histamine release, and so provides a convenient means of estimating mast cell degranulation (16). When human mast cells were reacted with live trichomonads, β-hexosaminidase release increased as a function of number of trichomonads, and TCM promoted β-hexosaminidase release with an efficiency similar to that observed with 5 × 106 live trichomonads (Figure 3). Furthermore, when mast cells were incubated with TCM

for 6 h, IL-8 and TNF-α production increased more than with CM (Figure 4a,b). Because of the possibility that these cytokines were present in the TCM, we also examined the production of cytokine mRNAs and found that IL-8 and TNF-α mRNA levels in the mast Copanlisib chemical structure cells were also increased preferentially by exposure to TCM (Figure 4c). Neutrophils are known to play an important role in inflammatory responses by virtue of their ability to perform a series of effector functions that collectively represent a major mechanism of innate immunity against injury or infection. Neutrophil infiltration is thought to be primarily responsible for the cytological changes observed

in trichomoniasis (12,17). We investigated whether culture supernatants Lumacaftor ic50 of mast cells incubated with TCM for 6 h (M-TCM) had chemotactic activity for neutrophils. Medium alone (C), culture supernatant of mast cell alone (M) and culture supernatant of mast cell activated with CM (M-CM) had similar chemotactic activities. M-TCM stimulated neutrophil migration in a concentration-dependent manner, and M-TCM was more effective at each concentration than the corresponding TCM concentration (Figure 5), indicating that mast cells may play a role in neutrophil migration. Adhesion of T. vaginalis

to VECs is a prerequisite for the establishment of infection and plays an important role in the pathogenesis of trichomoniasis (2,3,9). Kucknoor et al. (9) examined transcriptional changes during the initial stage of T. vaginalis adhesion to VECs and showed upregulation of genes related to inflammation, such as IL-8, MCP-1, COX-2 and FN. Until now, it has not been known how these inflammatory mediators influence the inflammation caused by T. vaginalis. 17-DMAG (Alvespimycin) HCl Therefore, the aim of this study was to see whether supernatants of human vaginal epithelium cells incubated with live T. vaginalis (TCM) influenced inflammatory cell migration and activity. We indeed found that such culture supernatants attracted mast cells and stimulated them to release of β-hexosaminidase and cytokines, which could subsequently induce neutrophil migration. Mast cells are key effectors of allergic inflammation in peripheral tissues. However, because of the discovery that they play a critical role in protection during acute infection, they are now considered as primary inducers of both innate and adaptive immune responses (10,18). Mast cells are generally present in mucosal tissues, which are continuously exposed to foreign antigens including pathogens and allergens (19).

As the CD45− VCAM-1+ cells express 4–1BBL, a VCAM-1+ stromal cell is a plausible candidate for the radioresistant cell that provides 4–1BBL

to sustain memory CD8+ T cells. Previous results have shown that 4–1BBL contributes signals to maintain CD8+ memory T cells in the absence of their specific antigen in vivo [29]. To address whether the effect of 4–1BBL requires that its receptor, 4–1BB, is expressed Selleck Tofacitinib on the T cells, we first asked whether 4–1BB-deficient mice have the same decrease in CD8+ T-cell responses to influenza as previously determined for 4–1BBL-deficient mice [28]. We find that, similarly to results reported for 4–1BBL-deficient mice [28], the CD8+ T-cell response to influenza virus is unimpaired at the peak of the primary response in 4–1BB-deficient mice, but shows a statistically significant decline in the frequency of CD8+ T cells at 3 weeks post infection (Supporting Information Fig. 1A). This decline in CD8+ T cells late in the primary response correlates with a proportional decrease in secondary response upon rechallenge (Supporting Information Fig. 1A and B). To determine whether this defect was T-cell intrinsic, we generated mixed BM chimeras, in which only the BM-derived αβ T cells lack 4–1BB and compared these with completely 4–1BB-sufficient mice (Fig. 1A). We used MAPK inhibitor a ratio of 1:4 4–1BB−/− to TCRα-deficient BM, so that all the T cells would lack 4–1BB, but only 20% of the

non-T cells would be 4–1BB-deficient. Consistent with the result obtained in the complete 4–1BB−/− mice

(Supporting Information Fig. 1A), 4–1BB on αβ T cells is dispensable for the primary CD8+ T-cell response to influenza virus (Fig. 1B and Supporting Information Fig. 2 for gating strategy). Upon secondary challenge with influenza A/PR8, the absence of 4–1BB on αβ T cells results in a significant decrease in the nucleoprotein (NP)-specific CD8+ T-cell response in the spleen and BM (Fig. 1C). For Thiamine-diphosphate kinase the mice used in Figure 1C, we had also confirmed the absence of a defect in primary response based on analysis of blood T cells at day 7 following priming (data not shown). Thus, 4–1BB expression on the αβ T cells is required for the maximal CD8+ T-cell recall response to influenza virus. Our finding that 4–1BB is required on αβ T cells for maximal recall responses coupled with our previous findings that 4–1BBL is required for the maintenance of memory CD8+ T cells in the absence of antigen in vivo [29], suggests that 4–1BB on T cells binding to 4–1BBL in mice contributes to the maintenance of the memory CD8+ T cells. Thus, 4–1BB should be expressed on T cells in unimmunized mice. A recent study reported a low level of 4–1BB expression on CD44Hi CD8+ T cells in the BM of unimmunized mice [32]. Here, we extend this analysis to examine 4–1BB expression on CD8+ and CD4+ CD44Hi T cells from BM as well as the spleen and LN of unimmunized WT mice, using 4–1BB−/− mice as a staining control.

“
“Apoptotic cell death has been considered an underlying mechanism in acute lung injury. To evaluate the evidence of this process, apoptosis rate was determined in effector cells (alveolar macrophages, neutrophils) and target cells (tracheobronchial and alveolar epithelial cells) of the respiratory compartment upon exposure to hypoxia and endotoxin stimulation in vitro. Cells were exposed to 5% oxygen or incubated with lipopolysaccharide (LPS) for 4, 8 and 24 h, and activity of caspase-3, -8 and -9 was determined. Caspase-3 of alveolar macrophages was increased

at all three time-points upon LPS stimulation, while PI3K Inhibitor Library screening hypoxia did not affect apoptosis rate at early time-points. In neutrophils, apoptosis was decreased in an early phase of hypoxia at 4 h. However, enhanced expression of caspase-3 activity was seen at 8 and 24 h. In the presence of LPS a decreased apoptosis rate was observed at 8 h compared to controls, while it was increased at 24 h. Tracheobronchial as well

as alveolar epithelial cells experienced an enhanced caspase-3 activity upon LPS stimulation with no change of apoptosis rate under hypoxia. While increased apoptosis rate is triggered through an intrinsic and extrinsic pathway in alveolar macrophages, intrinsic signalling is activated in tracheobronchial epithelial cells. The exact pathway pattern in neutrophils and alveolar epithelial acetylcholine cells could not be determined. These data clearly demonstrate that buy RAD001 upon injury each cell type experiences its own apoptosis pattern. Further experiments

need to be performed to determine the functional role of these apoptotic processes in acute lung injury. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause severe respiratory failure and death in critically ill patients. The development of ALI/ARDS is associated with several clinical disorders, including direct pulmonary injury from pneumonia and aspiration as well as indirect pulmonary injury from trauma or sepsis [1]. Although knowledge about mechanisms leading to ALI/ARDS has increased, no specific and successful treatment options exist to date and thus the mortality rate remains high in patients with ALI/ARDS [2]. The airway compartment with alveolar macrophages and epithelial cells, such as tracheobronchial and alveolar epithelial cells, is a physiological barrier to a variety of environmental agents, including gases, particulates and microbes. Alveolar macrophages are located at the air–tissue interface in the lung and are therefore the first cells which interact with inhaled organisms and antigens [3].

KA1 and SH25 strains demonstrated the highest parasite burdens, while DE5 strain showed intermediate and DA39 strain displayed the lowest load of the viable parasites in the LN cells culture with statistically significant differences compared with the mice infected with the other strains.

Data were also in agreement with the results obtained in our previous study, suggesting the induction of the lowest and the highest load of the parasite by DA39 and SH25 strains in draining LN of BALB/c mice, respectively, 8 weeks post-infection [14]. Gamma interferon is the key feature of Th1 response and mediates macrophage LY2157299 activation against L. major. Induction of this cytokine mRNA expression describes the direction of a protective immune response. These data show that all four strains elicited a distinct pattern of Ifng mRNA expression and among them DA39 strain induced augmented levels of the transcript expression at 16 h, rising to a peak of 127 FI at 40 h post-infection. Although the expression of Ifng transcript in draining LN cells at the late period showed rather lower rate at W1 and W5, the increase in this cytokine transcript in LN of mice injected with DA39 and SH25 strains at W3, Wnt inhibitor and all four strains at W8 displayed a tendency towards a Th1 immune response. Interestingly, DA39 strain

which induced the lowest load of parasites eight weeks post-infection had an ability to elicit higher expressions of Ifng mRNA than other strains at 40 h, W3 and somehow W8 post-infection. These results show consistency with results Glutamate dehydrogenase of Kabaier et al.

who observed higher production of IL-4 and lower generation of IFN-γ by isolates with higher virulence [11]. Moreover, a burst of Il2 transcript expression was documented in the early phase of the infection which peaked to 113 FI at 40 h post-infection in draining LN cells of the mice inoculated with DA39 strain. These data showed consistency with the increase of Ifng mRNA expression at early phase of the infection, particularly with the results observed at 40 h post-infection (Fig. 2a). Likewise, the results obtained were in agreement with reports of Gumy et al., suggesting an early production of Il2 transcript in BALB/c mice [24]. Indeed, there is a bulk of evidence suggesting that IL-2 might be one of the cytokines of Th1 response [6]. However, a controversy exist which correlates the effect of IL-2 on induction of Th1 or Th2 responses in the literature, and recent studies have documented the important role of IL-2 along with IL-4 in mediating Th2 responses [24]. Meanwhile, our results showed disagreement with the suggestion of Gumy et al. about the preceding of Il2 mRNA expression to Il4 transcript expression at early stages of the infection [24].

To evade destruction by the host immune system, the spirochete has developed evasion strategies such as antigenic variation of surface proteins. Zhang and co-workers first

described antigenic variation of a 35-kDa surface lipoprotein in check details B. burgdorferi which they termed VlsE (variable major protein-like sequence; Zhang et al., 1997). VlsE is similar to the well characterized variable major protein (Vmp) of the relapsing fever Borrelia (Barbour, 1993). The vlsE locus is encoded on the lp28-1 plasmid and consists of the vlsE expression site and 15 silent cassettes (Zhang et al., 1997). Within each silent cassette, there are six variable regions (VR-I through VR-VI) and six highly conserved regions. Importantly, the VlsE regions of variability are located on the membrane distal portion of the protein, which is more likely to

come in contact with antibody during mammalian infection (Eicken et al., 2001). During mammalian infection, regions of the expressed vlsE cassette are replaced with regions of the silent cassettes through a gene conversion mechanism that can result in numerous vlsE sequence products (Zhang et al., 1997; Zhang & Norris, 1998a, b). Sequence variation occurs in all six of the variable regions of the expression site, but the sequence of the silent cassettes is conserved (Zhang et al., 1997; Zhang & Norris, 1998a, b). In mice, variability of vlsE is observed as early as 4 days postinfection (Zhang & Norris, 1998b). These changes Selleck Bafilomycin A1 continue during the duration of the infection and occur at greater frequencies at later time points postinfection (Zhang & Norris, 1998b). Interestingly, clonal populations of B. burgdorferi grown in vitro or maintained within ticks retain the parental vlsE sequence, and sequence variation in immunocompetent mice occurred at a greater rate as compared to variation of vlsE in SCID mice (Zhang & Norris, 1998b). These data suggest that conversion is dependent on mammalian factors and that selection of vlsE variants occurs in the presence of an intact

immune response (Zhang et al., 1997; Zhang & Norris, 1998b; Indest et al., 2001). Presence of lp28-1, the vlsE encoding plasmid, is correlated with an intermediate infectivity phenotype of B. burgdorferi in which the spirochetes are unable to persist tetracosactide in tissues (Purser & Norris, 2000; Labandeira-Rey & Skare, 2001). However, strains lacking lp28-1 are able to infect and persist in SCID mice, suggesting that lp28-1 is required for B. burgdorferi to survive in the presence of an intact immune system (Labandeira-Rey et al., 2003; Purser et al., 2003). A B. burgdorferi strain lacking vlsE expression was developed by deleting the region encoding this locus (Bankhead & Chaconas, 2007). Importantly, the VlsE-mutant strain demonstrated a phenotype similar to an lp28-1-deficient B. burgdorferi strain. The combined data suggest VlsE as an important virulence determinant of B. burgdorferi.