Loss of thymus cellularity is a common feature among inflammatory/infectious processes [24]. Moreover, it has been reported that when the cellularity of this organ is compromised, the number of peripheral cells infiltrating into the thymus considerably increases [4, 6, 18, 19]. Then, we speculated that available space could represent a crucial situation for cell migration to the thymus in inflammatory conditions. To test this hypothesis, we examined T. cruzi infected mice at two different times: before the parasitemia peak (BPP, between 9 and 11 days postinfection), where the part of resident thymocytes (especially double positive (DP) cells) are depleted, and during the parasitemia

peak (PP, between 12 and 14 days postinfection), when a larger number of thymocytes are depleted (Fig. 2A). As CD4+ and CD8+

cells are found GSI-IX supplier in the thymus as single positive thymocytes, it is difficult to discriminate between resident Neratinib datasheet and peripheral mature T cells; however, we and others have demonstrated that expression of CD44, an activation marker for T cells is preferentially expressed by mature T cells that enter the thymus [7, 17, 25] (Fig. 3A). Thus, we evaluated the percentage and the absolute number of CD44hi T cells present in the thymi of T. cruzi infected mice. As shown in Fig. 2, the percentage (Fig. 2B) as well as the absolute number (Fig. 2C) of CD44hi cells in the CD4+ or CD8+ single positive compartment significantly increase when the total cellularity of the thymus decreases (Fig. 2A) (compare old BPP and PP). Based on the high percentages of CFSE+ CD19+ cells that enter the thymus in the three inflammatory conditions evaluated (Fig. 1), we also analyzed the absolute number of B cells in the thymi of control or T. cruzi infected mice. Both the percentage and the absolute number of B cells increased (Fig. 2D) with the reduction in the cellularity of the organ (Fig. 2A). Interestingly, the kinetics of cell entry to the thymus varies depending upon the inflammatory/infection process being evaluated (after 3 days of LPS treatment, around

days 12–14 in T. cruzi infected mice and around days 6–7 in C. albicans infected mice). However, what they all have in common is the fact that cells enter the thymus when cellularity of this organ starts to diminish. Based on the later data, we speculated that any situation where the total thymocyte number is reduced would favor the entrance of peripheral cells to the thymus. To prove this hypothesis, we treated mice with dexamethasone (Dex) since it has been demonstrated that this hormone considerably decreases the cellularity of the thymus [26, 27]. We adoptively transferred CFSE splenocytes from LPS-treated mice into LPS- or Dex-treated recipient mice [26]. Even though the total cell number of thymocytes is highly diminished in both LPS- and Dex-treated mice, peripheral cells could enter the thymus only in LPS-treated mice (Fig. 2E).

Activating receptors have a short cytoplasmic tail with a positively charged amino acid residue within their transmembrane region that allows their association with ITAM-bearing adaptors (e.g. DNAX-activating protein (DAP) 12, FcεRIγ or CD3ζ) Ensartinib research buy 3. Upon ligand recognition and receptor clustering, ITAM become tyrosine phosphorylated and serve as docking sites for Src homology type 2 domain-containing protein tyrosine kinases such as ZAP-70 or Syk 4, 5. Recruitment and activation of protein tyrosine kinases and downstream effectors regulate calcium mobilization, transcriptional activation, cytokine production, migration,

proliferation and/or differentiation 6. In contrast, inhibitory receptors display

a longer cytoplasmic tail characterized by the presence of ITIM. Ligand-induced clustering results in tyrosine phosphorylation of ITIM that act as docking sites for SHP-1, SHP-2 or SHIP. Upon recruitment, tyrosine phosphatases become activated and dephosphorylate key signaling mediators of activation pathways such as Syk, CHIR-99021 cell line LAT, BLNK/SLP-76, Vav, PI3K and cytoskeletal structures, consequently downregulating the signaling cascade 6–8. The CD300 or immune receptor expressed by myeloid celsl (IREM) family of myeloid-associated receptors consists of at least five surface molecules that are encoded by genes located on human chromosome 17 (17q25) 9. CD300c (CMRF-35) was the first identified but has been thus far poorly characterized 10, 11. CD300a (IRp60) was shown to associate with SHP-1 and SHP-2, delivering inhibitory signals in human NK cells, mast cells, eosinophils and granulocytes 11–15. Metformin price CD300f (IREM-1) is another inhibitory receptor restricted to myeloid cells, capable of recruiting both SHP-1 and PI3K (p85α subunit) 16, 17. By contrast, CD300b (IREM-3 or hLMIR5) is a receptor mainly expressed

on myeloid cells delivering activating signals by interaction with DAP12 and DAP10 18, 19. We originally described CD300e (IREM-2), a monomeric 32 kDa glycoprotein with a single extracellular Ig-like domain, expressed by mature monocytes and peripheral blood myeloid DC (mDC). CD300e displays a transmembrane lysine residue allowing the receptor to associate with DAP12 in transfected African Green monkey kidney fibroblast cell line (COS-7) cells. Engagement of CD300e-induced NFAT transcriptional activity in rat basophilic leukemia-transfected cells and TNF-α release in human monocytes 20 suggesting that CD300e may constitute an activating receptor. In this study, we investigated in detail the function of CD300e in human monocytes and mDC by using an agonistic anti-CD300e mAb. Overall, our data support the notion that CD300e constitutes an activating receptor capable of regulating inflammatory responses.

The results from the studies were each independently significant, with P values ranging from <0·01

Liproxstatin-1 mw to 0·04. Because each study was reported as independently significant, we did not perform a formal meta-analysis on these data. Serum MBL-level data from active TB versus controls are shown graphically in Fig. 4. The consistent finding of higher MBL serum levels in patients with TB than uninfected controls suggests strongly that high MBL levels are associated with active TB disease. Our meta-analysis of accessible, published data has demonstrated no statistically significant association between MBL2 genotype and pulmonary TB infection. Review of studies considering MBL levels has, however, demonstrated a consistent increase in MBL levels in patients with tuberculosis. There are a number PLX-4720 of mechanisms that could account for this discrepancy between MBL levels and MBL2 genotype and their associations with TB. First, MBL2 genotype involving structural gene polymorphisms alone is a poor predictor of serum MBL

levels. Therefore the direct assessment of MBL phenotype through measurement of blood levels may be the best way to reveal an association between MBL sufficiency and predisposition to TB from the available data. Perhaps the most plausible explanation, however, is that MBL is elevated in active tuberculosis infection as part of an acute-phase reaction. If this is so, then MBL would not appear to be involved significantly in host susceptibility to tuberculosis infection. In an attempt to investigate these alternative explanations, we performed additional ad hoc subgroup analysis on studies that reported complete MBL2 genotypic profile, including promoter regions. The small sample of this subgroup analysis does

not permit significant conclusions to be drawn from the lack of association between complete MBL2 genotype and TB susceptibility; however, were such results repeated in Oxaprozin larger studies it may provide additional support for the hypothesis that MBL is not involved in tuberculosis infection and elevated MBL levels seen in patients with TB represent its acute-phase response. Although some studies have suggested that MBL may not have a significant overall acute-phase response, patients with wild-type MBL2 genotypes have been generally found to have raised MBL levels in this setting [30]. This is consistent with the study populations included in this meta-analysis, where the proportion of patients homozygous for wild-type MBL2 accounted for 92% of the populations where both MBL levels and genotypes were available. In these populations, therefore, the acute-phase properties of MBL are likely to be dominant. This contrasts with other studies of the acute-phase change seen in septic patients who had a higher frequency of MBL2 variant alleles [36]. Support for this conclusion can be seen in studies where MBL levels have been studied in the acute-phase reaction. Thiel et al.

DCs were originally

defined by Steinman and Cohn[113] on their ability to HDAC inhibitor stimulate in an allogeneic mixed leukocyte reaction. In 2011, Ralph Steinman was awarded a Nobel Prize in Physiology or Medicine for demonstrating the significance of this cell type in health and disease. Based on this original definition, it was recently postulated that DCs should be exclusively defined to antigen-presenting cells that reside in T cells areas of the spleen and lymph node and lack expression of the common macrophage markers F4/80 and CD11b.[78] Confusion has primarily arisen while characterizing DCs in non-lymphoid organs because many assume that what is apparent in the lymphoid organs is also evident in non-lymphoid

organs, and what is true during steady state is also valid during inflammation. However, these assumptions should be avoided, and instead a combination of cellular origin, anatomical location, function and phenotype applied to all settings to successfully distinguish between both populations. The early events that lead to monocyte differentiation into macrophages and/or DCs in the injured kidney is an area of ongoing research as recently reviewed.[114] Overall studies suggest that Ly6Chi inflammatory monocytes are the major cell population recruited to the injured kidney regardless of the insult, and their cell fate decision is highly dependent on the learn more nature of the injury. In non-immune mediated injury models such as UUO and IR, a greater proportion of monocytes differentiate into macrophages, whereas in immune-mediated renal injury, the majority of monocytes give rise to DCs. Tissue injury also appears to be caused fundamentally by Ly6Chi monocyte-derived macrophages, while renoprotection is mediated by resident DCs. Important insights into monocyte recruitment and differentiation have been gained from analysing selleck kinase inhibitor the murine model of renal IR injury. Li et al.[67] identified two distinct subsets of F4/80-positive cells that differentiated from Ly6Chi inflammatory monocytes within 3 h of reperfusion. They were

phenotypically and functionally characterized as CD11bhiF4/80lo macrophages and CD11bloF4/80hi DCs. By 24 h post-IR injury, the number of Ly6Chi inflammatory monocytes peaked in the kidney, but had developed a more macrophage-like phenotype that corresponded with acute renal dysfunction. In contrast, the total number of CD11bloF4/80hi DCs remained unchanged at the same stage, and failed to initiate a pro-inflammatory response despite exhibiting high TNF-α expression.[67] In a mouse model of UUO, Lin et al.[92] demonstrated that Ly6Chi inflammatory monocytes enter the kidney and differentiate into three specific macrophage populations that differ in Ly6C expression (Ly6Chi, Ly6Cint and Ly6Clo).

First, efficacy was demonstrated in a multiple-dose treatment selleck inhibitor study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti-mC5aR-treated mice. Then, the mechanism of action was examined by looking for early effects of anti-mC5aR treatment in single-dose treatment studies. We found that 48 h after single-dose treatment with anti-mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore,

dose-setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated

rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in rheumatoid arthritis patients, by identifying selleckchem potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR. “
“Preterm labor and birth continue to pose a significant challenge to physicians in the obstetrics and neonatal fields. Until specific and effective therapeutic treatments are developed to prevent preterm labor, the best means of reducing preterm birth rate is early detection and diagnosis. However, current approaches to predict preterm labor have had variable success in the clinical setting. In this review, we discuss several limitations of using biomarkers from biological samples to predict preterm labor. In addition, we propose strategies for improving our ability to predict preterm labor, as well as directing therapies

that are best suited to the underlying cause of preterm labor. Preterm Anidulafungin (LY303366) labor and birth are responsible for the majority of neonatal morbidity and mortality including cerebral palsy, blindness, and deafness, resulting in an annual cost of over 26 billion dollars in 2005.[1] Not surprisingly, a tremendous amount of effort has been expended to counter the rising trend in preterm births. Clinicians are under increasing pressure to practice ‘evidence-based medicine,’ which is often mistakenly interpreted as ‘randomized controlled trials’. Using that criterion, there is a paucity of effective interventions or predictive tools to stop preterm labor. For example, the lack of evidenced-based data suggests we abandon interventions such as IV hydration and reduced activity, which many clinicians believe (at least anecdotally) are effective in some patients. Moreover, the data from ‘the evidence’ appear inconsistent, at least on the surface. For example, midtrimester short cervix (<25 mm) has been shown to be a risk factor for spontaneous preterm birth.

First, unlike mHFE+ skin grafts

onto DBA/2 mHfe KO mice (whether TCR-transgenic or not), with local and coinciding antigenic charge and inflammatory reaction, the anti-mHFE TCR-transgenic CD8+ T cells were i.v. injected into Rag 2 KO DBA/2 mHFE+ mice in a noninflammatory context (LPS was administered on day 12, at which time the CFSE experiment established that the injected cells had already disappeared). Second, albeit HFE is broadly expressed, its expression in antigen-presenting cells in particular dendritic cells is relatively limited [[4]] and HFE is expressed in a variety of nonantigen-presenting cells including cells of the liver, an click here organ endowed with strong tolerogenic properties [[35]]. It should however be stressed that the absence of GVHD

when HFE is the sole molecule targeted by a monoclonal CD8+ T-cell population does not exclude that in other situations (additional minor histocompatibility mismatches, polyclonality of the injected cells, etc.) an HFE mismatch would not contribute to GVH reactions, as documented for HY mismatches in human clinic [[36]]. Whereas most anti-mHFE TCR-transgenic T lymphocytes are blocked in the thymus at the CD4+ CD8+ double positive stage in DBA/2 mHFE+ mice, some cells escape deletion and are found in the periphery. These cells express a low level of the transgenic TCR, are CD4−, CD8−, CD25− and approximately 50% of them express NK-cell markers, NKp46, and DX5. These cells differ from Treg cells phenotypically (CD4−, FoxP3−) and functionally (no suppressive activity) but share similarities (co-expression of NK-cell markers, reduced amounts of TCR) with conventional NKT cells [[37]]. However, LEE011 unlike NKT cells, they do not express the PLZF transcription factor [[38]] and produce neither IL-4, nor IFN-γ but produce IL-6, IL-10, and hepcidin. They must therefore have been differently reprogrammed. Whether these cells are a residual and not a functional population of lymphocytes simply “parked” in the periphery or, as their production of IL-6 and hepcidin (two key regulators of iron metabolism) may suggest, contribute to iron homeostasis is an open question. From that point of view it has to be stressed that similar cytokine productions

were not observed with H-2 Db-restricted anti-HY TCR transgenic T lymphocytes from male mice that similarly downregulate their TCRs Ergoloid [[34]]. Several other observations support the notion that the immune system plays a regulatory role in iron metabolism. Iron overload in Rag/β2m double KO is more accentuated than in β2m single KO mice [[39]] and, in hemochromatosis patients, an inverse correlation has been observed between CD8+ T-cell numbers and disease severity [[40]], a possible consequence of the recently documented production of hepcidin by T lymphocytes [[41]]. Having established that mHFE is an autonomous histocompatibility antigen for mHfe KO and mHfe-C282Y mutated mice, it remains to be seen whether the same is true for hereditary hemochromatosis patients.

They also reported that there was no difference in the expression of TRPM8 in urinary bladder afferent neurons between control and bladder outlet obstruction rats.48 Shibata et al.49 also reported that dichotomizing afferents of L6-S1 dorsal root ganglion neurons that innervate the skin and bladder were constantly observed with retrograde neuron tracers in rats. In situ hybridization experiments revealed that approximately 8.0% of the double-labeled cells expressed transient receptor

potential channel melastatin member 8 (TRPM8) transcripts in the dorsal root ganglia. Cold and menthol stimuli to the skin generated bladder nerve responses conducted through dichotomizing axons, which significantly decreased in the presence of the TRPM8 blocker BCTC. Taken together, they concluded that TRPM8-expressing APO866 clinical trial sensory neurons with dichotomizing axons projecting to the skin and bladder may be responsible for the urinary urgency evoked by cold stimuli. Cold, heat, pain, and touch sensations on the skin are passed to the thalamus via the dorsal root and spinothalamic tract (Fig. 9). In this pathway, there must be some type of interaction with the micturition

control system. The adrenergic nervous system, unmyelinated c-fibers, and TRPM8 may play important roles in this pathway (Fig. 9).15,17,47–49 Further studies are required to clarify the mechanism of the cold stress-induced increase in urinary frequency and the roles of TRPM8 in the micturition control system. The authors of this paper have no financial or commercial interests to disclose. “
“Objectives: The clinical efficacy and safety of 75 mg/day of naftopidil, an α1-adrenargic receptor antagonist, was assessed MK0683 chemical structure MycoClean Mycoplasma Removal Kit in patients with benign prostatic hyperplasia (BPH). Methods: A total of 28 patients (mean age, 71.1 years; range, 46–86 years) with BPH were studied. Inclusion criteria were: (i) International

Prostate Symptom Score (IPSS) ≥8; and (ii) quality of life (QOL) index ≥3. IPSS, QOL index, Overactive Bladder Symptom Score (OABSS), and bladder diary (urinary frequency in daytime and nighttime, frequency of urinary incontinence and urgency) were evaluated before and 4 weeks after treatment with naftopidil at 75 mg/day. Results: Total IPSS and QOL index were significantly decreased after treatment. Total OABSS tended to decrease after treatment, with significant improvements in the “urgency” parameter. From the bladder diary, urinary frequency in daytime and nighttime and frequency of urgency were significantly decreased after treatment. Total IPSS and QOL index in patients with previous treatment were significantly improved after treatment, with significant improvements in the “incomplete emptying,”“poor flow” and “nocturia” parameters of IPSS. One case with a mild adverse effect of dizziness was encountered. Conclusion: These results suggest that administration of naftopidil at 75 mg/day was safe and effective for patients with BPH, regardless of the presence of previous treatment.

i. We suggest that in

early CKD patients with diabetic nephropathy, consumption of a carbohydrate-restricted, low-iron-available, polyphenol-enriched (CR-LIPE) diet may slow the progression of diabetic nephropathy (2C). j. We recommend that overweight/obese patients with CKD should be prescribed caloric restriction under the management of an appropriately qualified dietitian. A reduction in weight can mean improvement of CKD (1C). l. We suggest adults with early CKD consume a balanced diet rich in fruits and vegetables, as these appear to reduce blood pressure and have renoprotective effects comparable to sodium bicarbonate (2C). m. We suggest adults with early CKD consume a Mediterranean style diet to reduce dyslipidemia and to protect against lipid peroxidation and inflammation (2C). n. We suggest adults with early CKD consume a diet rich in dietary fibre that is associated with reduced inflammation CDK inhibitors in clinical trials and mortality in patients with CKD (2D). o. We suggest that patients with CKD be encouraged to undertake Ivacaftor ic50 regular physical exercise that is appropriate

for their physical ability and medical history (2B). q. We recommend that patients with CKD stop smoking to reduce their risk of CKD progression and cardiovascular risk (1C). r. There is no specific evidence for alcohol consumption in patients with CKD. However, we suggest the recommendations made by the NHMRC Australian Guidelines to Reduce Health Risks from Drinking Alcohol be applied to patients with early CKD (2C). s. We suggest patients with CKD minimize their intake of cola beverages to a maximum of one glass (250 ml) or less of cola per day (2C). t. We suggest that patients drink fluid in Unoprostone moderation. For most patients with early CKD, a daily fluid intake of 2–2.5 L (including the fluid content of foods) is sufficient, although this might need to be varied according to individual circumstances (2C). Note: There is no convincing evidence to date that pushing oral fluid intake beyond this amount, except in states of excessive fluid loss (e.g. sweating or diarrhoea), is beneficial for long-term

kidney health. a. We recommend that either ACEI or ARB should be used as first line therapy (1B) c. We recommend BP ≤ 140/90 (1B) a. We recommend that either ACEI or ARB should be used as first line therapy (1A) d. We recommend a blood pressure target of ≤130/80 in all people with diabetes (1B) We recommend that patients with early CKD (stage 1–3) should be treated with statin therapy (with or without ezetimibe) to reduce the risk of atherosclerotic events (1A). We recommend that patients with early (stage 1–3) CKD because of type 1 or type 2 diabetes mellitus aim to achieve a HbA1c target of approximately 7.0% or 53 mmol/mol* (1B). We recommend caution against intensively lowering HbA1c levels appreciably below 7.0% in view of demonstrated increased risks of hypoglycaemia (1B) and possibly death (1C).

, CA, USA) per immunization, while fenugreek immunized mice received 4.2 mg fenugreek protein with 10 μg CT per immunization. Blood samples before challenge were obtained from v. saphena lateralis on day 33/34. Challenges were performed with a large dose of one of the protein extracts (peanut, lupin, fenugreek and soy). Based on previous experience, the doses were 25 mg p.o. and 5 mg intraperitoneally (i.p.). Challenge

with the primary allergen was carried out by both routes in the two models. In the lupin model, challenge with cross-reactive legumes was performed both p.o. and i.p., but as the responses did not seem to differ with regards to anaphylactic reactions or mast cell responses between the two challenge routes in this model, only i.p. LY294002 purchase challenges were performed with cross-reactive legumes in the fenugreek model. The p.o. dose was divided into two equal doses given 30 min apart. Some mice were not challenged and are referred to as immunized only. Control mice were either treated with CT only (sham immunized) or left untreated (naïve mice) (Table 1). Daporinad purchase Assessment of clinical anaphylactic reactions.  Anaphylactic symptoms were evaluated continuously from the start of the challenge until 30 min after the i.p. challenge or the second p.o. challenge. The scoring system described by Li et al. [27] was used: 0 – no symptoms; 1 – scratching and rubbing around the nose and head; 2 – puffiness

around the eyes and mouth, diarrhoea, pilar erecti, reduced activity and/or decreased activity with an increased respiratory rate; 3 – wheezing, laboured respiration, cyanosis around the mouth and tail; 4 – no activity after prodding or tremor and convulsion; 5 – death. The mice were exsanguinated immediately after the assessment of

the anaphylactic reactions. The clinical anaphylactic reactions were analysed by Ordinal Regression Ketotifen using Statistical Package for Social Sciences (spss version 14.0; SPSS Inc., Chicago, IL, USA). Because of a quasi-complete separation in the data, contingency table analysis (Fisher exact test) was used to validate the statistics of the Ordinal Regression. Serum mouse mast cell protease-1 (MMCP-1) assay.  Serum levels of mouse mast cell protease-1 (MMCP-1) were determined at exsanguination with an ELISA kit (Moredun Scientific Ltd., Edinburgh, UK) and performed according to the manufacturer’s instructions. Results were analysed by one-way anova on log transformed data, and significant differences between the groups were determined by the Holm-Sidak method. Results are presented as box-plots showing the median, 25th–75th percentile, 10th–90th percentile and outliers. Total and allergen-specific IgE analyses.  Due to the inclusion of several sub-studies (Table 1), sera were analysed for total IgE before (49 mice), after (67 mice) or both before and after challenge (89 mice).

This work was supported by the Roche Research Fund for Biology, the Bonizzi-Theler Stiftung, the GEBERT-RÜF-STIFTUNG, the Swiss National Science Foundation, the Vontobel Foundation, and UBS AG on behalf of a client. Conflict of interest: The authors declare no financial

or commercial conflict of interest. “
“Mast cells are proposed to be one of the targets for mucosal vaccine adjuvants. We previously demonstrated that mucosal adjuvants containing IgG immune complexes could activate connective tissue mast cells enhancing immune responses. Here we suggest that mucosal mast cells (MMC) may also contribute to augmentation of antigen-specific XL765 order immune responses following treatment with antigens complexed with IgG. We demonstrated that both bone marrow (BM)-derived cultured MMC and tissue resident MMC incorporated ovalbumin (OVA) at a greater level in the presence of anti-OVA IgG. Co-culture of OVA/IgG-pulsed BM-derived

MMC with splenocytes from OT-II mice promoted OVA-specific activation and proliferation of T cells, a process known as cross-presentation. Furthermore, BM-derived cultured MMC underwent apoptosis following treatment with IgG immune complexes, a feature that has been described to favour phagocytosis of mast cells by professional antigen-presenting cells. This article is protected by copyright. All rights reserved. “
“Infections caused GDC 0068 by the L-NAME HCl leading nosocomial pathogen Staphylococcus epidermidis are characterized by biofilm formation on implanted medical devices. In a previous study, we found that ClpP protease plays an essential role in biofilm formation of S. epidermidis. However, the mechanism by which ClpP impacts S. epidermidis biofilms has remained unknown. Here, we show that the Spx protein accumulates in the clpP mutant strain of S. epidermidis and controls biofilm formation of S. epidermidis via a pronounced effect on the transcription of the icaADBC operon coding

for the production of the biofilm exopolysaccharide polysaccharide intercellular adhesion (PIA). Notably, in contrast to Staphylococcus aureus, Spx controls PIA expression via an icaR-independent mechanism. Furthermore, Spx affected primary surface attachment, although not by regulating the production of the autolysin AtlE. Our results indicate that ClpP enhances the formation of S. epidermidis biofilms by degrading Spx, a negative regulator of biofilm formation. Staphylococcus epidermidis, previously regarded as an innocuous commensal bacterium of the human skin, has emerged as one of the most frequent causes of nosocomial infection in recent years. Staphylococcus epidermidis may cause persistent infections by forming biofilms on implanted medical devices, such as central venous catheters, urinary catheters, prosthetic heart valves and orthopedic devices.