Together, the present finding supports the hypothesis that the ur

Together, the present finding supports the hypothesis that the ureteral obstruction leads to the alteration of renal vitamin D metabolic enzyme expression and calcium transporter abundance, which may secondarily induce the abnormality of vitamin D endocrine system

and bone health. “
“Lower preoperative haemoglobin and older age pose a risk for perioperative allogeneic blood transfusions (ABT). The presence of chronic find more kidney disease (CKD) is associated with low haemoglobin, greater bleeding and ABT utilization. The interaction between estimated glomerular filtration rate (eGFR) and haemoglobin on perioperative ABT, length-of-stay and mortality was assessed in 86 patients with CKD stage 3 or higher undergoing elective total knee or hip arthroplasty compared with 294 without CKD. Multivariate analyses for ABT risk with haemoglobin, eGFR, age, gender, duration of surgery and primary versus revision surgery were performed. Patients with CKD had lower preoperative haemoglobin and higher incidence of ABT. Haemoglobin

was independently associated with increased odds of ABT (0.74 (95% confidence interval 0.71–0.77), P = 0.001), but eGFR was not (0.98 (0.96–1.02), P = 0.089). Length-of-stay and 1 year mortality did not differ between non-transfused CKD patients and controls. Transfused CKD patients had significantly higher length-of-stay compared with transfused controls (25 ± 21 AZD2014 vs 19 ± 16 days, P < 0.0001), although 1 year mortality between transfused CKD patients and controls did not differ significantly. CKD alone, in the absence of anaemia, does not Sclareol predispose

to increased risk of ABT or length-of-stay in patients with mild-to-moderate CKD undergoing elective joint surgery. However, low haemoglobin is associated with increased ABT utilization and increased length-of-stay. Considering that 1 in 4 patients undergoing elective hip or knee arthroplasty has CKD, optimal preoperative patient blood management may improve outcome in this population. “
“It is not known whether nutritional status differs between Australian Aboriginal and non Aboriginal haemodialysis subjects. The aim of this study was to investigate the nutritional status of Australian Aboriginal and non-Aboriginal haemodialysis subjects at satellite dialysis centres. Seventy-six (25 Aboriginal, 51 non-Aboriginal) prevalent haemodialysis patients were enrolled in a 3-month cross-sectional study. Each month anthropometric and biochemical measurements were collected. Nutritional status (diet history, patient-generated subjective global assessment (PG-SGA), handgrip strength) was assessed by a dietitian. PG-SGA detected mild to moderate malnutrition in 35% of Aboriginal patients and 25% of non-Aboriginal patients.

Animal vital statistics are shown in Table 1 An N of 17 sham and

Animal vital statistics are shown in Table 1. An N of 17 sham and 13 PMMTM-exposed animals were used for the intravital preparation, and an N of 11 sham and 8 PMMTM-exposed animals were used for the isolated arteriole preparation (Table 1). All animal procedures were approved by the WVU Institutional Animal Care and Use Committee. Air was sampled at two sites within 1 mile of an active see more MTM site (Sundial, WV, USA). PM was collected on 35 mm 5 μm pore

size PTFE fiber-backed filters (Whatman, Springfield Mill, UK, Figure 1A) for 2–4 weeks. Air flow rate across the filters averaged 12 L/min. Following collection, the filters were stored at room temperature (20–25°C) and ambient humidity (10–30%) in the dark for 0.5–1 year prior to extraction. PM (Figure 1B) was removed from the filters by gentle agitation in 15 mL of ultrapure water (Cayman Chemical, Ann Arbor, MI, USA) in a glass jar for 96 hours. Storage and extraction of the particles from the filters are consistent with previously reported methods [14]. Aliquots of the particle suspension were dried down in 2 mL cryovials for 18 hours in a Speedvac (Savant, Midland, MI, USA). Total particle weight was determined by a microbalance (Metler-Toledo, Columbus,

OH, USA). Elemental concentration in atomic weight (ppm) was obtained from individual particles with a SEM (JEOL LTD., Tokyo, Japan) coupled with EDX technology (Oxford Instruments, Oxfordshire, UK). A filter sample (˜2 cm2) was obtained from a PTFE filter and mounted with double-sided DAPT mouse adhesive copper tape on a brass (Cu and Zn) specimen stub. Approximately four to five samples per selleck inhibitor filter and 20–25 individual particles per sample were randomly chosen for a total analysis of 100 particles per filter using the Spot & ID EDX Analysis Mode. An accelerating voltage of 20 kV was used and the working distance was set to 15 mm with a 120 seconds live time for X-ray acquisition. Particles 0.5–20 μm were analyzed and a quant optimization was performed on Cu. Analyses were performed on the PMMTM by a commercial laboratory (RTI International,

RTP, NC, USA). Briefly, pre-weighed PMMTM was resuspended into 5 mL of methanol and vortexed. The sample was then split into two equal volume aliquots for ICP-AES and IC analysis. ICP-AES analysis was performed via EPA method 3060C on material extracted using EPA method 3052. Sulfate IC analysis was performed by EPA method 300.0 with modifications for use on the Dionex ICS-3000 (Thermo Scientific, Sunnyvale, CA, USA) with eluent generation [44]. Standard reference material 1648a (St. Louis, MO, US Urban PM; NIST, Gaithersburg, MD, USA) was used as a quality control. The following metals and compounds were determined: Al, Ba, Ca, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Si, Sn, Ti, V, Zn, and SO4. Elements not appearing in Table 2 were below detectable limits.

CD38 mean fluorescence intensity (MFI) increased not only in CD14

CD38 mean fluorescence intensity (MFI) increased not only in CD14+ monocytes that became infected but also in monocytes in the same cultures that remained uninfected (Supporting Information Fig. selleck kinase inhibitor 4). These results indicate that exposure to HIV-1 is sufficient to cause upregulation of CD38 in peripheral blood monocytes in vitro and, taken together

with the observed effects of depleting HIV-specific IL-10+ CD8+ T cells, suggest that the latter could protect monocytes from activation by HIV-1 in vivo. Finally, we investigated whether the effects of HIV-specific IL-10+ CD8+ T cells on monocyte CD38 expression were IL-10-dependent. Treatment of CD8-depleted PBMCs with an IL-10 receptor (IL-10R) blocking antibody prior to co-culture overnight with CD8+ T cells led to a marginal

increase in monocyte CD38 expression, when compared with the effect of depleting HIV-specific IL-10+ CD8+ T cells. This could reflect incomplete receptor blockade on monocytes; alternatively, it could indicate RAD001 ic50 that this population may not mediate its effects solely through IL-10 production (Supporting Information Fig. 5). In this study, we have shown that a distinct subpopulation of HIV-specific CD8+ T cells contributes substantially to IL-10 production by PBMCs in chronic uncontrolled HIV-1 infection. The magnitude of this population was positively correlated with the magnitude of the IFN-γ response to the same HIV-1 antigens and the majority of the CD8+ T-cell subset co-produced IL-10 and IFN-γ upon short-term HIV-1 gag stimulation. However, a shift towards lone IL-10 production was associated with better virological control. Together, these observations suggest that a subset of HIV-1 gag-specific IFN-γ-secreting CD8+ T cells may have acquired the capacity to produce IL-10 in response to chronic viral replication, possibly as Adenosine a protective response to inflammation in the context

of ongoing antigenic stimulation. Their virtual absence in patients treated with an effective ART regimen is consistent with this notion, although this remains to be confirmed in a longitudinal study. Furthermore, their lack of a conventional Treg-cell phenotype contrasted with CMV-specific IL-10+ CD8+ T cells that were detected in some co-infected individuals and suggests that these populations have distinct ontogenies. Co-expression of IL-10 and IFN-γ by tissue-homing virus-specific T cells has been extensively reported in murine viral infection models and in human CD4+ T cells [11, 19, 25-28]. By contrast, human virus-specific CD8+ T-cell populations with dual IL-10-/IFN-γ-secreting capacity appear to be rare: to our knowledge, the only precedent for this is in Epstein-Barr virus (EBV) infected solid organ transplant recipients, in whom CD8+ Treg type 1 cells expressing FoxP3 could be induced in vitro by type-1-polarising DCs [11].

35 In this model, the effectiveness of ACEi in slowing the progre

35 In this model, the effectiveness of ACEi in slowing the progression of normoalbuminuria to microalbuminuria was based on only one randomized trial of 156 normotensive, Enzalutamide mw middle-aged Israeli people.14 This trial showed that ACEi therapy was associated with an absolute risk reduction of 12.5% CI: 2–23% over 6 years. The effectiveness of ACEi is slowing the progression of microalbuminuria to diabetic kidney disease was also based on one study by.13 In 94 normotensive middle-aged Israeli people with type 2 diabetes, AER increased over 5 years from 123 to 310 mg/24 h

in the placebo group, and from 143 to 150 mg/24 h in the enalapril treatment group, showing a significant reduction in the rate of change of AER (P < 0.05). In the model by Golan et al.35 the transition time from macroalbuminuria to ESKD was

extrapolated from data on people with type 1 diabetes.36 Potential costs factored into the model included screening for microalbuminuria and proteinuria, drug costs and expenses incurred in treating ESKD with either dialysis or transplantation. The model also considered the effects of treatment non-compliance on cost-effectiveness and adjusted outcomes for quality of life changes. Compared with waiting until overt proteinuria develops, treating microalbuminuria with ACEi was estimated check details to reduce overt proteinuria from 16.8 to 10.4%, ESKD from 2.1 to 1.9% and total mortality from 15.2 to 14.7% over 10-years.35 By comparison, treating all people with type 2 diabetes with an ACEi, rather than screening for microalbuminuria, reduced microalbuminuria from 25.3 to 18.2%, overt proteinuria from 10.4 to 9.0%, ESKD from 1.4 to 1.2% and isometheptene total mortality from 14.7 to 14.6% over 10-years.35 ACEi treatment of overt proteinuria in normotensive,

people with type I diabetes reduces the progression to ESKD by about 40%.36 The rate of progression from gross proteinuria to ESKD is similar in people with type 1 and type 2 diabetes.37 However, it can not be assumed that ACEi will have the same effect on the prevention of ESKD in people with type 2 diabetes as shown for people with type 1 diabetes. This is because of a greater contribution of age-related intrarenal atherosclerosis and glomerulosclerosis leading to a decline in the number of functioning glomeruli. It is important to appreciate that cost-effectiveness is critically dependent on the life expectancy of the population it is applied to. Thus, treating microalbuminuria in elderly people will be less cost-effective than treating younger people. Cost-effectiveness is also reduced if more liberal criteria are used to diagnose diabetes or if screened people are unlikely to take prescribed medications.35 Cost-effectiveness also depends on the cost of ACEi. Projections based upon the current cost of ACEi may underestimate cost-effectiveness considering that many of these agents will soon be off patent and presumably substantially cheaper.

EE has been demonstrated to induce beneficial cognitive effects i

EE has been demonstrated to induce beneficial cognitive effects in genetically targeted mouse models of AD [58–64]. The effects of EE on amyloid plaque formation/clearance EPZ-6438 ic50 have been found to differ widely in different studies [58,59,65]. However, as amyloid plaques (and neurofibrillary tangles) are primarily assessed as neuropathological markers, and a range of other molecular and cellular changes have been implicated in AD pathogenesis, an

understanding of the mechanisms mediating the beneficial effects of EE is likely to be found elsewhere. Other aspects of EE-induced benefits in AD mouse models have been addressed, including the issue of timing with respect to preventative and therapeutic effects [66,67]. The EE studies in AD mice have been extended to a range of different molecular, cellular and behavioural effects [67–73]. A recent study has implicated β2 adrenergic receptors in the beneficial effects of EE on hippocampal synaptic plasticity in AD mice [74]. One important aspect of the cognitive enhancing effects of EE is that these

have also been reported in wild-type rodents [7]. Thus, many of the cognitive enhancing effects of EE observed in animal models of AD may largely reflect a wild-type effect superimposed on an AD genotype. With this in mind, it is important to contemplate the kinds of changes that are induced at molecular and cellular click here levels by EE in wild-type rodents, and this will be discussed below. Increased physical exercise alone have been shown to have beneficial effects in AD mice [60,75–78], although a late exercise intervention in one transgenic AD mouse model did not exert cognitive enhancement [79]. However, cognitive stimulation

has also been found to constitute a major component of the beneficial effects of EE in AD mice [60,80]. This is crotamiton consistent with epidemiological and interventional clinical studies suggesting that enhanced cognitive stimulation and physical exercise may delay onset and possibly also slow progression of AD and other forms of dementia [81–84]. EE has also been demonstrated to induce beneficial effects in animal models of Parkinson’s disease (PD). PD is a neurodegenerative disease involving symptoms including tremor, rigidity, slowness of movement and gait problems, and can be associated with additional cognitive and psychiatric features. A key neuropathological hallmark is loss of dopaminergic neurones, particularly in the substantia nigra (SN). As for AD, the familial early-onset form of PD is less common, compared to sporadic late-onset PD, which constitutes the vast majority of cases. Another parallel with AD is that the genetics of familial PD is far better understood than the common sporadic form of the disease.

Results showed that 45 of the infants exhibited brief episodes of

Results showed that 45 of the infants exhibited brief episodes of bradycardia at the onset of arm-restraint. Group comparisons showed infants exhibiting bradycardia to have greater APO866 molecular weight emotional reactivity during the arm-restraint protocol, which included a shorter latency to cry, decreased orientation toward mother, increased escape attempts during restraint, greater intensity of crying, and longer duration of crying than non-bradycardiac infants. These findings suggest that bradycardia at the outset of a mild perturbation episode may signal infants’ attention to the emotional

content of novel dyadic interactions and the disruption of expectancies in ongoing interactions, leading them to become distressed more quickly, turn their attention away from mom, and attempt to escape the restraint with greater vigor. “
“Explanations of variability in long-term

recall typically appeal to encoding and/or retrieval processes. However, for well over a century, it has been apparent that for memory traces to be stored successfully, they must undergo MK0683 a post-encoding process of stabilization and integration. Variability in post-encoding processes is thus a potential source of age-related and individual variance in long-term recall. We examined post-encoding variability in each of two experiments. In each experiment, 20-month-old infants were exposed to novel three-step sequences in each of three encoding conditions: watch only, imitate, MycoClean Mycoplasma Removal Kit and learn to criterion. They were tested for recall after 15 min (as a measure of the success of encoding) and either weeks (1, 2, or 3: Experiment 1) or days (1, 2, or 4: Experiment 2) later. In each experiment, differential relative levels of performance among the conditions were observed at the two tests. The results implicate post-encoding processes are a source of variance in long-term recall. “
“Halberda (2003) demonstrated that 17-month-old infants,

but not 14- or 16-month-olds, use a strategy known as mutual exclusivity (ME) to identify the meanings of new words. When 17-month-olds were presented with a novel word in an intermodal preferential looking task, they preferentially fixated a novel object over an object for which they already had a name. We explored whether the development of this word-learning strategy is driven by children’s experience of hearing only one name for each referent in their environment by comparing the behavior of infants from monolingual and bilingual homes. Monolingual infants aged 17–22 months showed clear evidence of using an ME strategy, in that they preferentially fixated the novel object when they were asked to “look at the dax.” Bilingual infants of the same age and vocabulary size failed to show a similar pattern of behavior.

This study would be the first of its kind in the field


This study would be the first of its kind in the field

of human VL, as none of the reports dealt with human iNKT cells and their dynamics with the therapy. A belief was that CD1d-reactive cells must be expressing invariant TCR (Vα24 and Vβ11 in human) (1–3). In contrast, our finding suggests that all invariant TCR-expressing cells (iNKT) may not be solely reactive to the CD1d, especially in diseased condition, as evident from their proportional frequency (15). If CD1d-reactive NKT cells are approximately 0·2–0·4% of total lymphocyte, then what could be the reactivity of remaining iNKT cells? (approximately 1% of total lymphocyte). It indicates that all iNKT cells may not be CD1d buy AZD6738 reactive. Definition of human iNKT cells is further compounded by the strange observation

of a novel population with Vβ11+, but CD161− (Figure 1b,d). This population may be expressing other NK cell marker of NK cell recognition complex. Palbociclib But absence of a stimulatory/activating receptor CD161, which recognizes non-MHC ligand, potentiates possible function of this novel subset in a MHC-dependent manner. However, a detailed study is required in this regard. Duality in function of the enriched iNKT cells at the disease site will be crucial in dictating the disease outcome. Dichotomies in the functional behaviour of iNKT cells are in support for the existence of iNKT-1 (IFN-γ producing) and iNKT-2 (IL-4 producing), very similar to Th-1 and Th-2 (16). The antigen-specific response of these functionally divergent cells will be relevant in context of the pathology of VL. They may have some role in the early modulation/triggering of forthcoming immune response at disease site. This study was supported by Department of Biotechnology (Government 4-Aminobutyrate aminotransferase of India) for funding the work (Grant No.: BT/PR6737/Med/14/871/2005).

In addition, we thank the Council of Scientific and Industrial Research (CSIR), Government of India, for providing fellowship to Dr. Ambak K. Rai. The authors thank all the patients and control subjects who voluntarily agreed to participate in this study. We also thank Dr. Pradeep Dagur and Dr. Beenu Joshi, (JALMA, Agra, India) for helping in preparation of Leishmania antigen and extremely grateful to Dr. R. Viswakarma (NII, New Delhi, India) for providing LPG. Figure S1. MNCs derived from blood of patients were stained under various staining conditions (a) Preloaded CD1d dimer with aGalcer, but no secondary fluorescent antibody, (b) unloaded CD1d dimer, with secondary fluorescent antibody and (c) preloaded CD1d dimer with aGalcer, with secondary fluorescent antibody. Figure S2. MNCs were incubated with CD1d dimer under following conditions (a) Loaded CD1d dimer, no aIgG1 FITC, (b) unloaded CD1d dimer, aIgG1 FITC, (c) Loaded CD1d dimer (in 10× molar access), aIgG1 FITC and (d) Loaded CD1d dimer (in 20× molar access), aIgG1 FITC. Figure S3.

The capacity of LaAg to induce IL-10 secretion in PBMCs obtained

The capacity of LaAg to induce IL-10 secretion in PBMCs obtained from ATL patients, together with the generation of short-lived IFN-γ-producing CD4+T cells, could result in equilibrium between inflammatory and anti-inflammatory responses, allowing parasite clearance and lesion resolution, as observed

in the immunotherapeutic protocols tested so far. Currently we are performing multiparametric flow cytometry studies with PBMCs obtained from CL, ML and disseminated CL patients infected with L. braziliensis before and after therapy, in an attempt to find better immune parameters that could correlate with the clinical manifestation and effective healing of lesions. It is to be expected that understanding the induction of Leishmania-specific multifunctional T cells in the diverse clinical manifestations of ATL will help understanding of the complex immunopathogenesis of this neglected tropical disease, and bring new and important parameters selleckchem that can find more help in the selection of antigens or adjuvants that will have better chances of working in prophylactic or therapeutic interventions against human leishmaniasis. Based on our data, we are

very tempted to suggest that the quality of the Th1 response induced by L. amazonensis antigens, involving a poor generation of multifunctional CD4+T cells and a high proportion of IFN-γ single-positive CD4+T cells, in association with its well-known capacity of inducing IL-10 production [45–47,51,53,54], can be involved in the mechanisms responsible for the susceptibility to L. amazonensis observed in ATL patients and in experimental models. In this sense we have shown,

for the first time, that multiparametric flow cytometry can bring new Protein kinase N1 important aspects to the studies of ATL immunopathogenesis, and reinforce the importance of evaluating not just the magnitude, but the quality of a pathogen-specific Th1 immune response by multiple parameters at a single-cell level, to find better and more effective biomarkers of disease and protection. We thank the following funding agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – PAPES V), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ-APQ1) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for fellowship. We are also grateful to Dr Joseli de Oliveira Ferreira for critical reading of the manuscript. None. “
“Citation Martínez-García EA, Sánchez-Hernández PE, Chavez-Robles B, Nuñez-Atahualpa L, Martín-Márquez BT, Arana-Argaez VE, García-Iglesias T, González-López L, Gamez-Nava JI, Petri MH, Velazquez-Rodriguez J, Salazar-Paramo M, Davalos-Rodriguez IP, Daneri-Navarro A, Vázquez-Del Mercado M. The distribution of CD56dimCD16+ and CD56brightCD16− Cells are associated with prolactin levels during pregnancy and menstrual cycle in healthy women.

The expansion of the sex locus is also implicated by observations

The expansion of the sex locus is also implicated by observations in the other Mucorales species, which Epigenetics Compound Library manufacturer include an expansion of the sex locus to include the tptA and

rnhA gene promoters in M. circinelloides, a transposition of the arbA gene into the sex locus in R. oryzae and S. megalocarpus (or loss from other species/loci) and diversification of neighbouring rnhA genes and a gene encoding glutathione oxidoreductase in S. megalocarpus.[27] The sex locus of the Mucorales provides novel insights to understand sex chromosome evolution, in addition to the MAT loci of the dikarya, which provide insights on partner recognition and mating regulation. Furthermore, both humans and Mucoralean fungi utilise HMG proteins as key transcription factors for sex determination, and thus HMG proteins may be ancestral sex determinants. Mating between two different mating types produces progeny with a 1:1 segregation of both mating types. However, a significant mating type skew is found in pathogenic Mucor species. M. amphibiorum is a causal agent of ulcerative mycosis on platypuses in northern Tasmania in Australia. The

isolates from this area mainly represent (+) mating types and, in a toad mucormycosis model, the (+) mating types were more virulent than the (−) mating types.[36] The study found that the (+) mating types of M. amphibiorum caused more severe diseases in toads by producing spherules more check details rapidly than the (−) mating types. A similar mating type bias was observed in a plant pathogenic Mucorales. M. piriformis causes mucor rot in pear fruit and a study revealed that (+) mating type predominates over

(−) mating type in infected plants in Oregon pear orchards.[37] Interestingly, the (+) mating types produced larger lesions than the (−) mating types although both mating types can cause infections under laboratory conditions. In M. circinelloides, (−) mating type isolates tend to produce more virulent, larger spores than (+) mating type isolates, which produce less virulent, smaller spores; however, a subsequent finding suggested that the sexM gene in (−) mating type is not solely responsible for the spore oxyclozanide size difference in that sexMΔ mutants still produce larger spores.[24] Spore size could be controlled by SexP, by other genetic loci, or by other genetic loci acting in concert with SexM as a quantitative trait. Analogy is found in the human pathogenic basidiomycete Cryptococcus neoformans, in which the α mating type predominates in clinical and environmental samples (reviewed in [35]). In C. neoformans, unisexual reproduction explains this mating type bias[38, 39]; however, unisexual reproduction has not been described in the pathogenic Mucorales and currently there is no apparent explanation for the mating type bias in pathogenic Mucor species.

The reason for the efficient Cldn11 induction in BMDM is unclear,

The reason for the efficient Cldn11 induction in BMDM is unclear, although M-CSF, used to generate BMDM, and IL-4 have been shown before to co-regulate certain genes [30]. A summarized gene expression pattern of all adherence and tight junction proteins in macrophages is provided (See summary in Table 2, right columns). Although IL-4 significantly increases the mRNA levels of claudin-1, 2 and 11, this does not result in a detectable

expression of these proteins in macrophages. As a matter of fact, no reports of claudin protein expression in CDK inhibitor macrophages exist up to now, in contrast to related cell types such as LCs and DCs. Possibly, the claudin protein expression levels in macrophages are under the detection limit of the antibodies currently used. Alternatively, we cannot exclude that post-transcriptional, such as poor

mRNA stability, and/or post-translational regulatory mechanisms preclude high claudin levels in macrophages. For example, during epithelial reorganization, claudins are ubiquitylated and undergo degradation in the lysosomes [31]. A similar mechanism might be at play in macrophages, especially if the claudins are not engaged in TJ formation. In this respect, one could imagine that claudin proteins are stabilized in vivo when intimate interactions between macrophages and epithelial cells are formed. This could help to bring macrophages in close contact with epithelial cells or with other macrophages, a phenomenon that could be relevant in several situations: (1) in tumours where Ivacaftor ic50 fusion between macrophages and carcinoma cells might occur [32], (2) during wound healing where macrophages have to integrate in the epithelial sheet of the skin [33] and (3) during granuloma formation and the foreign body reaction where close contacts between macrophages have to be initiated to promote their fusion [29]. Interestingly, Lenzi et al. [34] reported the expression of cadherins and the tight junction–associated protein occludin during the Unoprostone process of granuloma closure. Yet, the lack of claudin proteins in our assays with IL-4-treated macrophages does not preclude their use as marker genes. Indeed, the macrophage activation status in a given pathological

condition is often evaluated by the detection of M1 versus M2 signature genes [4, 25, 26, 35]. Testing different M2 activators identified TGF-β as the most potent inducer of Cldn1 gene expression in macrophages. This finding is reminiscent of TGF-β’s central role in upregulating claudin-1 expression during IL-4-/GM-CSF-treated bone marrow cultures, ultimately giving rise to Langerhans cells [18]. The association of claudin-1 mRNA with the M2 activation status was further confirmed in vivo where high levels of Cldn1 induction were observed in TAM subsets from two mammary carcinoma models and in splenic macrophages isolated from the chronic infection stage of T. congolense infections. In both models, the implication of TGF-β seems plausible.