1) at ETS/IRF composite elements (EICE), description of AP-1/IRF composite elements (AICE) reveals how these factors function together to bind distinct elements

co-operatively, and may explain some of their distinct functions in T-cell subsets, dendritic cells and B cells. At AICE, combinatorial integration is possible through both varied AP-1 dimer composition and choice of IRF family co-factors. For example, IRF8 co-operates with BATF3/JUN to instruct homeostatic classical dendritic cell (cDC) differentiation, and with BATF/JUN during inflammatory cDC differentiation.[40] BATF/JUN and IRF4 co-operative binding at AICE motifs is required for instruction of Th17 GDC-0973 order differentiation and B-cell class switch recombination.[12,

30, 31, 40] Further, it is likely that co-operation of these AP-1/IRF complexes with different STAT family members can confer additional integration of environmental cues for interpretation of combinatorial motifs in regulatory DNA elements. Transcriptional programmes that integrate environmental signals with cell intrinsic features instruct cellular phenotypes, including plasticity. In this context, it is interesting to compare and contrast the transcriptional strategies of FOXP3 and RORγt in control of Treg and Th17 cell identity, respectively. Recent mechanistic insights into the transcriptional regulation of Foxp3 and Rorc and their targets explain some of the characteristics of the Treg and Th17 cellular phenotype. For example, both FOXP3 and RORγt have in common an activity that largely reinforces, stabilizes and maintains a chromatin PS-341 and gene activation landscape initiated

by ERFs. More specifically, these factors augment the expression of critical lineage-specific genes such as il2ra, ctla4, il10, il10ra, cd5, icos and notably, Foxp3 itself, in the case of FOXP3, and il17a, il17f, il1r1 and il23r for RORγt (Fig. 1). This target gene selection reflects the distinct behaviour and biology of Th17 and Treg cells. RORγt augments il23r expression in a positive feedback loop, as STAT3 signalling downstream of IL-23R activates Rorc expression. However, this feedback loop, and maintained expression selleck of Rorc and Th17 lineage fidelity, is dependent on the persistence of environmental IL-23 and transforming growth factor-β (TGF-β), and altered environmental signals, especially IL-12 and interferon-γ, can subvert Rorc expression and the Th17 transcriptional programme, converting cells to the Th1 lineage (Fig. 2).[42-44] In contrast, FOXP3 regulates its own expression upon engagement of a positive feedback loop following activation and CpG demethylation at a Foxp3-intronic enhancer (CNS2), a heritable feature of mature Treg cells, effectively buffering mature Treg cells from changes in environmental signals.[45] These differences may reflect important phenotypic features of these distinct cell types.

Syk was also required for Hrs ubiquitination catalyzed by c-Cbl E3 ligase. Syk-dependent regulation of Hrs covalent modifications, without affecting protein stability, controlled Hrs localization. The majority of phosphorylated Hrs forms were observed only in membrane compartments, whereas ubiquitinated Hrs was predominantly cytosolic, suggesting that both modifications might

impact on Hrs function. Together, these findings provide a major step forward in understanding how Syk orchestrates endocytosis of engaged immune receptors. The Syk/ZAP-70 family of protein tyrosine kinases (PTKs) plays an essential role in signaling through a variety of immune receptors (IRs), including the TCR and BCR, the high-affinity receptor for IgE (FcεRI), and the widely distributed receptors for IgG [1]. All these IRs contain selleck products multiple subunits; some, unique for

Panobinostat cell line each receptor, are used for ligand binding whereas others share a conserved ITAM that is rapidly phosphorylated by PTKs of the Src family upon IR aggregation, thus allowing signal propagation [2, 3]. IR-mediated signals also lead to a negative-feedback regulation by the internalization and delivery of engaged receptor complexes to lysosomes for degradation [4-11]. In the past years, we have concentrated our interest on the molecular mechanisms responsible for ligand-induced endo-cytosis of IRs, mainly focusing on the FcεRI that is constitutively expressed on the Nintedanib (BIBF 1120) membrane of mast cells and basophils. FcεRI is composed of an IgE-binding α chain, and the ITAM-containing β and γ subunits [12]. Upon FcεRI cross-linking, the β chain-associated

Src family PTK Lyn, phosphorylates β and γ-chain ITAMs allowing the recruitment and consequent activation of Syk [13]. The use of specific Syk inhibitors and Syk-negative cell lines demonstrated an obligatory role for this kinase in FcεRI-mediated mast cell responses [14-16]. However, limited data exist on the role of Syk as regulator of FcεRI endosomal trafficking [10, 11]. We have previously demonstrated that upon antigen stimulation FcεRI β and γ subunits are ubiquitinated through the combined enzymatic activities of the PTK Syk and the Ub ligase c-Cbl [17]. More recently, we provided evidence that this modification controls receptor internalization and sorting along the endocytic compartments through the action of Ub-binding adapters [11, 18, 19]. Notably, we have envisaged a critical role for the hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) in controlling the fate of internalized receptor complexes [11]. Hrs is a component of the endosomal sorting complex required for transport (ESCRT-0), resides into clathrin-coated microdomains of early endosomes where it recruits ubiquitinated cargo, and controls their delivery to multivesicular bodies [20, 21].

One of the obstacles in the implementation of clinical protocols using Tregs is their low frequency, 1–3% of total peripheral blood CD4+ T cells, and data (from animal models) which suggest that, for these cells to suppress immune responses, high doses of Tregs in relation to effectors is required [52, 53]. This means that for cellular therapy, it will almost certainly be necessary to use a polyclonal stimulus to expand Tregs in vitro. In this regard, the large-scale ex-vivo expansion of human Tregs by stimulation with anti-CD3 and anti-CD28 monoclonal antibody-coated beads and high-dose NVP-BGJ398 IL-2 has been demonstrated successfully [54]. However, effectors have the potential to proliferate

vigorously under such conditions, so that even a trace of effectors in the starting population can be expanded in high numbers. The injection of such cells would, therefore, be detrimental to the patient and may lead to rejection. Thus, it is essential to either initiate the expansion culture with highly purified Tregs (a challenge in view of the absence of a Treg-specific cell surface marker) or create culture conditions that favour Treg cell growth. Two different RG7420 purchase combinations of markers appear to be promising

for Treg isolation. The first seeks to isolate CD4+CD25hi Tregs, but with the addition of an antibody to select for CD45RA+ cells and so eliminate antigen-experienced or memory T cells [16]. The second combination also uses the CD4+CD25hi phenotype, but includes CD127 expression. The rationale for using CD127 as a marker for Treg isolation (as explained in earlier sections) is on the basis that in human Tregs there is a reciprocal expression of CD127 and FoxP3, and thus CD127 provides a sortable surrogate marker for FoxP3+ Tregs [24]. Moreover, the so-called ‘naive’ Treg population based on the co-expression of CD4 and CD45RA yield Tregs with a greater suppressive capacity than total CD25hi cells [55]. The reason for this became clear when Miyara et al. [22] noted the subpopulations of human FoxP3+ T cells and discovered that the CD25+CD45RA-FoxP3hi

cells contain many Th17 precursors. Furthermore, after 3 weeks of in-vitro expansion the CD45RA+-expanded Rolziracetam Tregs remained demethylated (compared to the CD127– Tregs that became methylated) at the Treg-specific demethylation region (TSDR), which is a conserved region upstream of exon 1 within the FoxP3 locus [completely demethylated in natural Tregs but methylated fully in induced Tregs and effector T cells (Teff)] [55, 56]. Such studies, therefore, support the isolation of Tregs based on CD45RA+ expression, bearing in mind that they are the most stable population for expansion and have the greatest expansion potential [16]. Despite such studies, one drawback is that the number of naive Tregs declines in the peripheral blood with age [57], and hence isolation based on CD127 expression may still be a practical approach.

At 7 months, by contrast, infants appear to react to the higher frequency of coronal consonants (Experiment 3a & b). The present study thus demonstrates that infants become sensitive to nonadjacent phonological dependencies between 7 and 10 months. It further establishes a change between

these two ages from sensitivity to local properties to nonadjacent dependencies in the phonological domain. “
“Effortful ABT-263 in vivo control (EC) refers to the ability to inhibit a dominant response to perform a subdominant one and has been shown as protective against a myriad of difficulties. Research examining precursors of EC has been limited to date, and in this study, infancy contributors to toddler EC were examined. Specifically, parent/family background variables (e.g., education, Selleckchem CYC202 income), maternal temperament, perceived stress, and internalizing symptoms were addressed, along with infant temperament: positive

affectivity/surgency (PAS), negative emotionality (NE), and regulatory capacity/orienting (RCO); and laboratory observation-based indicators of attention. Infant attention indexed by the latency to look away after initially orienting to the presented stimuli emerged as an important predictor of later EC, after accounting for other child and parent/family attributes, with shorter latencies predicting higher levels of EC. Mothers’ extraversion and parenting stress were the only parent/family attributes to significantly contribute to

the prediction of toddler EC, with the former promoting and the latter undermining the development of EC. Infant temperament factors were also examined as a moderator of parent/family influences, with results indicating a significant interaction between mothers’ EC and infant RCO, so that children with greater RCO and mothers high in EC exhibited the highest EC scores in toddlerhood. “
“Two preferential-reaching experiments explored 5- and 7-month-olds’ sensitivity to pictorial depth cues. In the first experiment, infants viewed a display in which texture gradients, linear perspective of the surface contours, and relative height in the visual field Tangeritin provided information that two objects were at different distances. Five- and 7-month-old infants reached preferentially for the apparently nearer object under monocular but not binocular viewing conditions, indicating that infants in both age groups respond to pictorial depth cues. In the second experiment, texture gradients and linear perspective of the surface contours were eliminated from the experimental display, making relative height the sole pictorial depth cue. Seven-month-olds again reached more often for the apparently nearer object under monocular, but not binocular viewing conditions.

The lateral abdominal wall is perfused predominantly from perforators arising from the intercostal vessels. Reconstruction of soft tissue defects involving the abdomen presents a difficult challenge for reconstructive surgeons. Pedicle perforator propeller flaps can be used to reconstruct defects of the abdomen, and here we present a thorough PD0325901 review of the literature as well as a case illustrating the perforasome propeller flap concept. A patient underwent resection for dermatofibrosarcoma protuberans resulting in a large defect of the epigastric soft tissue. A propeller flap was designed

based on a perforator arising from the superior deep epigastric vessels and was rotated 90° into the defect allowing primary closure of the donor site. The patient healed uneventfully and was without recurrent disease 37 months following reconstruction. Perforator propeller flaps can be used successfully in reconstruction of abdominal defects and should be incorporated

into the armamentarium of reconstructive microsurgeons already facile with perforator dissections. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“Single flap for complex hypopharyngoesophageal and anterior neck skin defect reconstruction is still a challenge for reconstructive surgeons. Herein, we present five patients, with advanced BMS-354825 in vivo hypopharyngeal cancer and anterior neck skin invasion, which received a single anterolateral thigh (ALT) fasciocutaneous flap for composite inner pharyngeal and outer skin defect reconstruction after wide composite resection. Two ALT flaps were divided into two distinct paddles supplied by two or more separate perforators, one part for reconstructing the inner pharyngeal defect and another for neck skin coverage. Three ALT flaps only supplied by one sizable perforator could not be divided and de-epithelization of mid-part had to be done to reconstruct both defects with the single flap. The results revealed survival of all flaps. There were no flap loss, fistulas, or bleeding complications. All patients recovered uneventfully and could eat a soft diet to regular diet postoperatively. In conclusion,

one-staged reconstruction of complex pharyngoesophageal and external skin defects after extensive oncological resection is feasible using a single ALT fasciocutaneous Etofibrate free flap. © 2011 Wiley-Liss, Inc. Microsurgery, 2011. “
“After injury of the brachial plexus, sensory disturbance in the affected limb varies according to the extent of root involvement. The goal of this study was to match sensory assessments and pain complaints with findings on CT myelo scans and surgical observations. One hundred fifty patients with supraclavicular stretch injury of the brachial plexus were operated upon within an average of 5.4 months of trauma. Preoperatively, upper limb sensation was evaluated using Semmes-Weinstein monofilaments. Pain complaints were recorded for each patient.

Paradoxically, inflammatory lipids and cytokines that promote VC have been shown to inhibit normal skeletal

mineralization.[35] Indeed, VC has been associated with loss of mineral from bone in patients with CKD and in post-menopausal women,[36, 37] and occurs simultaneously in some rodent models of arterial mineralization.[38] It is therefore possible to theorize that loss of bone-buffering selleck chemical capacity and increased flux of mineral through the bone-remodelling compartment and extracellular fluids may induce a state of mineral stress leading to increased CPP formation. This is consistent with our previous observation of a strong association between serum CPP fetuin-A levels and β-isomerized C-terminal telopeptides (a marker of bone turnover), independent of eGFR.[30] Although fetuin-A is widely regarded Protease Inhibitor Library as negative acute phase reactant,[39]

with hepatic synthesis being suppressed by pro-inflammatory cytokines,[40] we did not find a significant inverse relationship with serum CRP concentrations (r = −0.190, P = 0.084). This is consistent with previous reports in patients with pre-dialysis CKD,[41] but may reflect the fact that ‘total’ serum Fet-A concentrations are a heterogenous signal comprising free and complexed species that may be regulated differently. Moreover, while serum Fet-A RR (i.e. CPP), were strongly and positively correlated with CRP concentrations (r = 0.338, P = 0.002) supernatant Fet-A concentrations (i.e. free Fet-A) were strongly but inversely correlated with CRP (r = −0.409, P < 0.001) and weakly with albumin concentrations (r = 0.264, P = 0.032). find more Given the aforementioned putative vasculo-protective effects of free Fet-A, downregulation of hepatic production by inflammation is likely to potentiate the propensity for ectopic mineralization. Exceptionally high Fet-A RR were found in patients with CUA, implying a very severe perturbation of mineral regulation. Interestingly the fetuin-A knockout mouse develops lesions similar to those seen in CUA, suggesting that

if free Fet-A levels are depleted by the production of CPP we might see an acquired Fet-A deficiency.[8] Such a description was suggested by Brandenburg and colleagues when they described Fet-A concentrations reducing precipitately as CRP increased in a patient who developed CUA.[42] Consistent with some reports,[43, 44] but not others,[45] we observed significant reductions in serum total Fet-A concentrations during dialysis (mean 24% decrease). Somewhat unexpectedly, we also recorded reductions in CRP concentrations and serum Fet-A RR. Interestingly while the changes in serum CRP and total Fet-A were convincingly correlated (rho = 0.434, P = 0.008), there was no significant relationship between changes in CRP and Fet-A RR (rho = 0.050, P = 0.789). Given the size of CPP (50–200 nm), it seems unlikely that they would be removed by ultrafiltration; however, it is possible that particles may be retained by the membrane.

The results also showed that the proliferation of B6 spleen cells with IL-2 pre-incubation was significantly weaker than that of the controls

without IL-2 pre-incubation (P = 0·0025, Fig. 2b). SOCS-3 can inhibit the Th1-type polarization which plays a critical role in the pathophysiology of aGVHD [21,22,35,36]; therefore, we explored whether high SOCS-3 mRNA expression induced by IL-2 pre-incubation can inhibit Th1-type polarization in B6 naive CD4+ lymphocytes. According to the regularity of expression of SOCS-3 mRNA, we pre-incubated B6 naive CD4+ lymphocytes and B6 spleen cells, respectively, with IL-2 for 4 h before stimulation of allogeneic antigen-BALB/c spleen cells inactivated by mitomycin for 48 h. We then collected the supernatants to detect the levels of IFN-γ and IL-4. The results showed that expression of IFN-γ and Selleck Quizartinib IL-4 of B6 naive CD4+ lymphocytes was different between pre-incubation of the two groups with or without IL-2. The IFN-γ level in group pre-incubation with IL-2 was lower than that in group pre-incubation without IL-2 (P = 0·000, Fig. 3a). The IL-4 level in group pre-incubation with IL-2 was higher than that in group pre-incubation without IL-2 (P = 0·000, Fig. 3a). The expression selleck screening library of IFN-γ and IL-4 of B6 spleen cells was similar to that of B6 naive CD4+ lymphocytes (P = 0·002, and 0·000, respectively, Fig. 3b) We assessed suppressive function in vivo in an aGVHD mice model.

We used female BALB/C recipients and male B6 donors. All recipients received 5 Gy TBI as conditioning regimen. In group A (n = 9), B6 spleen cells (3 × 107 cells) were injected intraperitoneally into recipients as control. We first explored whether aGVHD was inhibited in the recipients (group B, n = 9) which received Ureohydrolase 3 × 107 B6 spleen cells pre-incubated with IL-2 before intraperitoneal injection. We found that the mean survival time of group B (14·4 ± 1·5 days) was not statistically different from that of group A (12·2 ± 3·1 days) (P = 0·3090, Fig. 4a). The scores of aGVHD symptoms between the two groups were

also not different (P = 0·7851). These findings suggest that IL-2 pre-incubation can up-regulate the expression of SOCS-3, but it was a short-lived gene product induced by IL-2 in lymphocytes. If the spleen cells with short-lived SOCS-3 did not receive allogeneic antigen in time, aGVHD could also not be inhibited; therefore, we projected another group (group D, n = 9) in which recipients received 3 × 107 B6 spleen cells which were presented with host-allogeneic antigen-inactivated BALB/C spleen cells for 72 h after IL-2 pre-incubation for 4 h. The results showed that aGVHD was inhibited significantly in group D. The mean survival time of group D was 44·1 ± 23·8 days, which was longer than that of group A (P = 0·0042, Fig. 4b). The score of aGVHD in group D was lower than that in group A (P = 0·0046).

Vα2+, Vα12+ and Vα2Vα12-double positive cells were identified in gated CD4+CD25highCD127lowFOXP3+ Treg and in CD4+CD25−/lowCD127+FOXP3− Tconv, and used to calculate the frequencies of %dual TCR cells

as described elsewhere 21 (Fig. 1C). To determine surface expression levels of TSLPR on MDCs, PBMCs were stained with mAbs specific for CD11c, CD123, HLA-DR, TSLPR, and the lineage cocktail (Lin, mAbs specific for CD3 (T cells), CD14 (monocytes), CD16, CD56 (natural killer cells), and CD19, CD20 (B cells). Labeled PBMCs were first gated for HLA-DR+Lin−, and further analyzed for expression of CD11c and CD123 to identify CD11c+CD123− MDC. Finally, TSLPR-MFIs were determined on gated MDC; Fig. 1D. PBMCs were isolated from 10–50 mL of peripheral blood by density gradient centrifugation with Ficoll-Hypaque (Biochrom AG, Berlin,

Erlotinib Germany). click here Total Treg and Tconv were immunomagnetically separated as described previously 2, 37, 38. IL-7 levels in serum samples were measured using a highly sensitive enzyme-linked immunosorbent assay (Quantikine-HS, Human IL-7 Immunoassay; R&D, Abingdon, UK), according to the manufacturer’s instructions. Samples were assayed in duplicate. For quantitation of sIL-7Rα in serum samples an in-house two-step ELISA was established, according to the protocol described by Rose et al. 39. In short, a microtiter plate was coated with a mouse anti-human IL-7Rα mAb (clone 40131), and – after blocking with PBS/0.05% Tween 20 – incubated with 200 μL undiluted serum overnight at room temperature. A biotinylated goat anti-human

IL-7Rα mAb, streptavidin-HRP and TMB substrate were used for detection and visualization of sIL-7Rα with a detection limit of 0.5 ng/mL. Serial dilutions of recombinant human IL-7Rα-Fc chimera protein served as positive next control and were used for creation of a standard curve. All antibodies and reagents were purchased from R&D. Genomic DNA was extracted from 105–106 PBMC cells using a QIAamp DNA Blood Mini Kit (Qiagen, Düsseldorf, Germany) according to the manufactures’ protocol. Screening for the MS-associated rs6897932 SNP within the IL-7RA gene was performed by using a TaqMan® predesigned SNP genotyping assay (Applied Biosystems, Foster City, CA, USA). PCR reactions were performed and analyzed as described by the manufacturer utilizing an Applied Biosystems 7500 Real-Time PCR System. In vitro proliferation assays were performed as previously described 2, 37. In brief, 105 freshly isolated Tconv were incubated alone or in co-culture with 2.5×104 total Treg (Tconv/Treg ratio 4:1) and polyclonally activated by addition of soluble anti-CD3 (1 μg/mL) and anti-CD28 mAbs (1 μg/mL). After 4 days, cells were pulsed for 16 h with 1 μCi of 3[H]-thymidine per well. After harvesting T-cell proliferation was measured with a scintillation counter.

The crosstalk between the innate and adaptive

immune systems is exemplified by responses involving marginal zone (MZ) B cells or invariant NKT (iNKT) cells. Indeed, these lymphocyte subsets mount very early, innate-like adaptive responses after recognizing microbial carbohydrate and glycolipid antigens via both germline-encoded and somatically recombined receptors [[3-5]]. B cells confer immune protection by producing antibody molecules, also known as immunoglobulins (Igs), which can recognize antigen through either low- or high-affinity binding modes. Bone marrow B-cell selleck chemicals precursors generate Ig recognition diversity by undergoing V(D)J gene recombination, an antigen-independent process that utilizes recombination activating gene (RAG) endonucleases to juxtapose noncontiguous variable (V), diversity (D) and joining (J) gene fragments into functional V(D)J genes encoding the antigen-binding V region of Ig molecules (reviewed in [[6]]). After further maturation events, multiple subsets of mature B cells co-expressing IgM and IgD emerge from GSI-IX research buy the

bone marrow and colonize different compartments of secondary lymphoid organs to initiate the antigen-dependent phase of B-cell development. In general, conventional follicular B cells, which are also called B-2 cells, predominantly participate in T-cell-dependent (TD) antibody responses to highly specific determinants usually associated with microbial proteins (reviewed in [[7]]). TD responses unfold in the germinal center of lymphoid follicles and generate high-affinity antibodies through a TD pathway that involves activation of B cells by follicular helper T (TFH) cells. This germinal center-associated

T-cell subset expresses the inducible T-cell costimulator (ICOS) receptor, the chemokine receptor CXCR5, the programmed cell death-1 (PD-1) inhibitory receptor and the transcription factor Bcl6 [[8-15]]. TFH cells provide help to B cells via CD40 ligand (CD40L) and cytokines such as IL-21, IL-4, and IL-10 [[16-19]]. However, recent findings indicate that follicular antibody responses further involve additional T-cell subsets, Mannose-binding protein-associated serine protease including follicular regulatory T (TFR) cells and iNKT cells [[4, 5, 20-22]]. Unlike follicular B cells, certain subsets of extrafollicular B cells such as B-1 cells, splenic MZ B cells (also referred to as IgM memory B cells in humans) and bone marrow perisinusoidal B cells predominantly give rise to rapid T-cell-independent (TI) antibody responses to highly conserved carbohydrate and glycolipid determinants associated with microbes [[3, 23-30]]. TI antibody responses usually unfold at the mucosal interface or in the splenic MZ and generate polyspecific and low-affinity antibodies through a TI pathway involving the interaction of B cells with DCs, macrophages, and granulocytes [[3, 30-34]].

, 1997; Casjens et al., 2000). Although the B. burgdorferi chromosome is rather small (approximately one megabase), the complexity and large sizes of many of the plasmids (some larger than 50 kb) greatly expand the DNA coding capacity of this spirochete. At the same time, however, it is currently poorly understood what role surface proteins encoded by genes on the various plasmids contribute to virulence and/or disease pathogenesis. The data accumulated thus far overwhelmingly support the hypothesis that plasmid-encoded proteins

are important in Lyme disease pathogenesis buy Buparlisib and could encode antigens that are important virulence factors and/or potential vaccinogens for Lyme disease. Given that the first vaccine developed for Lyme disease was generated against the fairly well conserved, plasmid-encoded OspA, it seems likely that PF-01367338 the identification of another outer surface protein that is well conserved throughout borrelial genospecies would be a viable candidate for a developing a new vaccine molecule. This review outlines the outer surface proteins that have been identified thus far in various borrelial species, although the main focus is on the type

strain B. burgdorferi strain B31. The outer surface proteins described below fall into two main categories, lipid-modified outer surface proteins that are anchored to the outer leaflet of the outer membrane through their lipid moieties (e.g. OspA, OspB, OspC, OspD, OspE, OspF, DbpA, DbpB, CspA, VlsE, BptA, and several others with no known function) and outer surface proteins that have one or more transmembrane domains that anchor them into the outer membrane (e.g. P13, P66, BesC, BamA, Lmp1, and BB0405). The sections following provide a detailed examination of what is currently known about outer surface lipoproteins and membrane-spanning OMPs of B. burgdorferi. The B. burgdorferi genome Diflunisal encodes several lipoproteins that are localized to the surface of B. burgdorferi (Fraser et al., 1997; Casjens

et al., 2000). The surface lipoproteins of B. burgdorferi are now well recognized as important virulence determinants. As mentioned previously, because of the extracellular nature of this pathogen, surface lipoproteins play an important role in virulence, host–pathogen interactions, and in maintaining the enzootic cycle of B. burgdorferi. Several borrelial surface lipoproteins have been identified that bind host proteins and promote the adherence to host cells. For instance, B. burgdorferi lipoproteins bind host glycosaminoglycans (GAGs), decorin, and fibronectin. Furthermore, lipoproteins have been implicated in evasion of the host immune response through antigenic variation and evasion of complement deposition.