Single-cell suspensions of 1 × 106 cells in a 50 μl or 100 μl of whole blood were washed with fluorescence activated cell sorter (FACS) buffer [phosphate-buffered saline (PBS) supplemented with 2% FBS and selleck products 0·02% sodium azide] and then preincubated with rat anti-mouse CD16/CD32 (clone 2.4G2) to block Fc binding. Specific antibodies were then added to the samples and incubated for 30 min at 4°C. Stained samples were then washed and fixed with 2% paraformaldehyde

for cell suspensions or treated with BD FACS lysing solution for whole blood. At least 50 000 events were acquired on LSRII or FACSCalibur instruments (BD Biosciences). Data analysis was performed with FlowJo (Tree Star, Inc., Ashland, OR, USA) software. Cytokine production by human CD4 and CD8 T cells Sunitinib in vivo was quantified using the BD Cytofix/Cytoperm Kit Plus GolgiStop (BD Biosciences), according to the manufacturer’s instructions. Splenocytes were recovered from the indicated mice at 12 weeks after implant of fetal tissues. Red blood cells were lysed and 1 × 106 cells were then left unstimulated or stimulated with phorbol myristate acetate (PMA) (0·5 μg/ml) and ionomycin (0·5 μg/ml) in the presence of GolgiStopTM (0·1 μg/ml) for 4 h at 37°C in 5% CO2. Cells were then fixed and permeabilized using Cytofix/Cytoperm solution and stained with monoclonal antibodies

(mAb) to interferon (IFN)-γ (clone 4S.B3; eBioscience), IL-2 (clone MQ1-17H12; eBioscience), IL-17A (clone eBio64DEC17; eBioscience) and IL-22 (clone IL22JOP; eBioscience). Stained samples were analysed as described above. CD4+ human Treg were identified in the blood of NSG–BLT mice by staining with antibodies specific for human CD25 (clones

MA-251 and 2A3), CD127 (clone A019D5) and forkhead box protein 3 (FoxP3) (clone Niclosamide 236A/E7). For staining, 100 μl of whole blood were washed with FACS buffer and then preincubated with rat anti-mouse FcR11b. Antibodies specific for human cell surface markers (CD45, CD3, CD4, CD25 and CD127) were added to the samples and incubated for 30 min at 4°C. Stained blood samples were then treated with BD FACS lysing solution for whole blood. Cells were incubated in eBioscience fixation/permeabilization buffer for 60 min and stained with antibodies specific for human FoxP3 in eBioscience permeabilization buffer for 60 min. Stained samples were analysed as described above. Heparinized blood samples from engrafted mice were centrifuged and the plasma was stored at −80°C. Human IgM and IgG levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit (Bethyl Laboratories, Inc., Montgomery, TX, USA) according to the manufacturer’s instructions and an EMax Endpoint ELISA microplate reader (Molecular Devices, Sunnyvale, CA, USA).

The lowest dose achieved in these patients did not correlate with patient weight, frequency of administration, disease duration or pretherapeutic level of disability, and the amplitude of dose reduction was independent of disease duration. An important question for neurologists to ask is how to balance the dose reduction with the risk of the patient’s condition

relapsing. Kuitwaard et al. evaluated IVIg pharmacokinetics selleck chemicals in 174 GBS patients receiving 0·4 g/kg/day for 5 days, and noted that the peak serum IgG concentration occurred 2 weeks after treatment, although with a high variability between patients [13]. When the patients were separated into quartiles according to the increase in serum IgG concentration [cut-off values of ΔIgG MG-132 supplier for quartile 1: <3·99 g/l (n = 43); quartile 2: 3·99–7·30 g/l (n = 45); quartile 3: 7·31–10·92 g/l (n = 43); and quartile 4: >0·92 g/l (n = 43)], those in the lowest quartile had a more severe clinical outcome (P < 0·001) in a number of measures, including clinical deficits, poor outcome, higher frequency of mechanical ventilation and time to reach a GBS disability score of 2, indicating that these patients would benefit from a higher dose of IVIg. A more recent pharmacokinetic study described 25 CIDP patients with active but stable

disease in whom the dose of IVIg had been optimized individually Interleukin-2 receptor [14]. Serum IgG levels were measured 5 min after infusion and compared with baseline measurements. The change in IgG levels was associated with IVIg dosage, but not treatment frequency, and both inter- and intrapatient variability was low,

leading the authors to conclude that constant serum IgG levels are required to stabilize CIDP patients. Similarly, when evaluating serum IgG levels in MMN patients receiving a cumulative dose of 2·0 g/kg for 5 days, wide variation was observed in total IgG and change in IgG levels between patients [15]. When comparing responders (defined as an increase in muscle strength of at least one Medical Research Council point in minimally two muscle groups) with non-responders, the authors noted that at each time-point (1 day, 5 days or 3 weeks after treatment) the change in IgG levels was higher in the IVIg responders than in the non-responders. The pharmacokinetic studies indicate that it is important to maintain serum IgG levels in order to achieve disease stability in patients with neurological disorders, and increasing dose frequency may assist with this goal. For example, a reduction in the IVIg treatment interval from 3-weekly to weekly administration may enable lower dosing while achieving higher serum IgG trough levels [16].

It is also possible that mycobacterial infection itself suppresses Th1, IL-17- and IL-22-producing CD4+ T cells or increases Th2 and regulatory T cells, which may limit the protective immune responses. IFN-γ-, IL-17- and IL-22-producing CD4+ T cells in individuals with active TB infection can be induced

by mycobacterial antigens (Fig. 3). Although not significant, a greater number of mycobacteria-specific IL-17- and IL-22-producing CD4+ T cells compared to the unstimulated cells were found in the latent group than in the active TB group. Although more numbers of patients need to be examined, differential IFN-γ, IL-17 and IL-22 responses could potentially improve our ability to distinguish between buy CHIR-99021 latent and active TB infection particularly when a clinical diagnosis is not straightforward [36]. We have shown for the first time that IL-22 is expressed in granulocytes. Interestingly, while intracellular IL-22 protein could be detected, IL-22 mRNA was undetectable in the resting granulocytes. PMA/ionomycin stimulation induced the expression of both IL-22 mRNA as well as intracellular IL-22 protein in granulocytes. The presence of IL-22 selleck products protein in the absence of detectable mRNA is not a unique phenomenon, as other cytokines such as IL-4 [37], IL-8 [38],

macrophage-inflammatory protein 2 (MIP-2) [39], granules and chemokines are also preformed and released rapidly upon stimulation of granulocytes [40,41]. In fact, constitutive expression of MIP-2 mRNA in bone marrow was shown to give rise to peripheral neutrophils with preformed MIP-2 protein [39]. Surprisingly, IL-22-expressing granulocytes in the peripheral blood were found to be higher in healthy controls than in latent TB individuals and even more so in active TB patients. This may be Nintedanib (BIBF 1120) due to localization of IL-22-producing granulocytes in affected

tissues. It is also possible that M. tuberculosis may affect the expression of IL-22 in vivo by inhibiting the synthesis of IL-22. Further studies are needed to investigate IL-22 gene regulation in neutrophils. Although the biological functions of IL-22 have been studied [22,42–45], the regulatory pathway for IL-22 expression is not well characterized. Our preliminary results suggest that neither pathogen-associated molecular patterns including TLR-2, TLR-4 and TLR-9 nor cytokines such as IL-6 and TGF-β, which are known to induce Th17 differentiation [8–10]-induced IL-22 expression in granulocytes (data not shown). We performed comprehensive analysis of a large number of cytokines (IL-1β, IL-2, IL-5, IL-6, IL-8, IL-4, IL-10, IL-12, IL-17, IL-22, IFN-γ, TNF-α and TNF-β) following mycobacterial stimulation of PBMCs and in a set of serum samples from individuals with latent and active TB infection. Our results show clearly that individuals with latent TB infection express differentially a number of proinflammatory and immunoregulatory cytokines.

MHC class I tetramers specific for NP118 and GP283 were prepared using published protocols [[58, 59]]. Significant differences between two groups were evaluated using a two-tailed Student’s t-test. We sincerely thank all members of the Harty laboratory for helpful discussion. Supported by NIH grants AI46653, AI150073, and AI42767. The authors declare no commercial or financial conflicts of interest. “
“Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston,

MA, USA Astragalus polysaccharides (APS), extracted from the root of Astragalus membranaceus, a traditional Chinese medicinal herb, have extensive pharmacological and strong immunomodulatory effects. In this study, the potential adjuvant effect of APS on humoral and cellular immune responses to hepatitis B subunit vaccine was investigated. JQ1 mouse Coadministration of APS NVP-AUY922 molecular weight with recombinant hepatitis B surface antigen significantly increased antigen-specific antibody production, T-cell proliferation and CTL (cytotoxic T lymphocyte) activity. Production of interferon-γ (IFN-γ), interleukin-2 (IL-2) and IL-4 in CD4+T cells and of IFN-γ in CD8+T cells were dramatically increased. Furthermore, expression of the genes PFP, GraB, Fas L and Fas were up-regulated; interestingly, expression of transforming growth factor

β (TGF-β) and the frequency of CD4+CD25+Foxp3+ regulatory T cells (Treg cells) were down-regulated. Expression of Toll-like receptor 4 (TLR4)

was significantly increased by administration of APS. Together, these results suggest that APS is a potent adjuvant for the hepatitis B subunit vaccine and can enhance both humoral and cellular immune responses via activating the TLR4 signaling pathway and inhibit the expression of TGF-β and frequency of Treg cells. Hepatitis B is a potentially life-threatening liver disease caused by hepatitis B virus (HBV) infection. It is a global health problem and the most serious type of viral hepatitis (Chisari & Ferrari, 1995). More than 350 million people worldwide are chronic HBV carriers, and 1–2 million people die each year due to the consequences of chronic hepatitis B (Rehermann, 2005). To date, the commercial recombinant hepatitis B surface antigen (HBsAg) vaccine has been widely used, and has become an effective strategy for preventing HBV buy HA-1077 infection. However, the vaccine primarily induces the antibody response and Th2-biased immune response, but elicits relatively weak cell-mediated immune responses, particularly the antigen-specific CTL response. Therefore, it is unable to clear the virus in the infected cells (Zhang et al., 2009; Geurtsvan et al., 2008). Astragalus membranaceus (Huangqi) is a well-tolerated and nontoxic traditional medicinal herb that is used as a therapeutic agent to treat many diseases in China (Luo et al., 2009; Cui et al., 2003). Astragalus polysaccharides (APS), the major component in the root of A.

However, the mechanisms of GCI formation are not fully understood. Cellular machinery for the formation of aggresomes has been linked to the biogenesis of the Lewy body, a characteristic α-synuclein-containing inclusion of Parkinson’s disease and dementia with Lewy bodies. Here, we examined whether GCIs contain the components of aggresomes by immunohistochemistry. Regorafenib datasheet Methods: Sections from five patients with MSA were stained immunohistochemically with antibodies against aggresome-related proteins and analysed in comparison with sections from five patients with no neurological disease. We evaluated the presence or absence

of aggresome-related proteins in GCIs by double immunofluorescence and immunoelectron Vorinostat molecular weight microscopy. Results: GCIs were clearly immunolabelled with antibodies against aggresome-related proteins, such as γ-tubulin, histone deacetylase 6 (HDAC6) and 20S proteasome subunits. Neuronal cytoplasmic inclusions (NCIs) were also immunopositive for these aggresome-related proteins. Double immunofluorescence staining and quantitative

analysis demonstrated that the majority of GCIs contained these proteins, as well as other aggresome-related proteins, such as Hsp70, Hsp90 and 62-kDa protein/sequestosome 1 (p62/SQSTM1). Immunoelectron microscopy demonstrated immunoreactivities for γ-tubulin and HDAC6 along the fibrils comprising GCIs. Conclusions: Our results indicate that GCIs, and probably NCIs, share at least some characteristics with aggresomes in terms of their protein components. Therefore, GCIs and NCIs may be another manifestation of aggresome-related inclusion bodies observed in neurodegenerative diseases. “
“Fasciculation and elongation protein zeta-1 (FEZ1) is a critical regulator Etoposide mw of dopaminergic neurone differentiation and dopamine release. However, to date, few studies evaluating the expression patterns of FEZ1 in Parkinson’s disease (PD) have been reported. The aim of this study was to investigate the expression and cellular localization of FEZ1 in a rat model of PD and to explore the role

of FEZ1 in PD pathogenesis. Male Sprague–Dawley rats were randomly divided into two groups: a PD group and a sham group. A model of PD was established by injecting 6-Hydroxydopamine Hydrobromide (6-OHDA) into the right medial forebrain bundle of rats. Sham-lesioned rats were infused with equivalent amounts of saline and served as controls. The expression levels of FEZ1 mRNA and protein in striatum and substantia nigra were examined by real-time polymerase chain reaction (PCR) and by Western blot analysis respectively. Immunohistochemistry was performed to identify the cellular localization of FEZ1 in sham-lesioned and PD rats. Western blot and real-time PCR analyses demonstrated that FEZ1 was present in normal rat brain striatum and substantia nigra. After the 6-OHDA injection, FEZ1 expression gradually increased, peaked and then decreased.

In addition to improved efficacy, specific combinations of agents could be designed to reduce side effects of treatment. The use of agents with different, yet complementary, mechanisms could facilitate dose reductions of drugs known to have toxicities at their conventionally prescribed doses. This could offer considerable advantages in T1D, where the risk : benefit ratio of a new therapy must always be compared https://www.selleckchem.com/products/pexidartinib-plx3397.html with that of daily

insulin injections. Thus, in autumn 2009, the Immune Tolerance Network (ITN), in concert with the Juvenile Diabetes Research Foundation (JDRF), convened a Type 1 Diabetes Combination Therapies Assessment Group to identify and discuss the various challenges and key opportunities

for combination therapies in T1D, and develop a framework of potential initiatives that will accelerate their clinical development. A key goal of the discussions was to establish a ranked list of promising ABT-263 in vivo combination therapies that will be priority targets for development through these initiatives. To date, there has been little clinical experience evaluating combinations of immunomodulatory agents for T1D; two published trials yielded disappointing results. A study of exenatide and daclizumab (anti-CD25 MAb; Zenapax, Hoffman-La Roche Ltd, Basel, Switzerland) was designed to examine whether stimulating insulin secretion during blockade of IL-2 signalling STAT inhibitor in effector T cells would affect endogenous insulin production in patients with long-standing T1D (21·3 ± 10·7 years). It is possible that the study aim was overly ambitious, because neither agent has shown efficacy in this setting. Perhaps not surprisingly,

the results showed that the combination of intensified insulin therapy, exenatide and daclizumab did not induce improved function of any remaining β cells [18]. Another combination evaluated by Type 1 Diabetes TrialNet examined two doses of daclizumab combined with daily mycophenolate mofetil (CellCept, Roche) in new-onset patients. This combination failed to show any benefit in terms of maintenance of stimulated C-peptide and was halted due to futility [19]. At present, the Immune Tolerance Network is also piloting a combination therapy targeting the IL-2 axis (IL-2 and Rapamycin; Proleukin and Rapamune/Sirolimus from Prometheus Laboratories Inc., San Diego, CA, USA, and Pfizer, New York, NY, USA, respectively) on the basis of a preclinical report of prevention of spontaneous T1D onset in non-obese diabetic (NOD) mice [20]. The mechanism of action of this combination is believed to involve a shift from T helper type 1 (Th1)- to Th2- and Th3-type cytokine-producing cells due to the selective deletion of autoreactive Th1 cells.

In MS patients, CSF and serum levels of TNF-α are elevated compared Peptide 17 with healthy subjects, and a rise in TNF-α in PBMCs has also been shown to precede clinical relapses 25, 42. TNF-α signaling through the neurotrophin receptor p55 in neurons and glia can mediate glutamate toxicity or lead to the activation of apoptotic signaling cascades (NF-κB, JNK, or p38 pathway) 42, 43. Notably, estradiol’s protective effect in EAE has been

attributed in part to its ability to inhibit the production of proinflammatory cytokines such as TNF-α from peripheral immune cells, and this has been shown to be mediated through ER-α 43, 44. Our results demonstrating an ER-β ligand-mediated GSK126 manufacturer reduction TNF-α in DC in the CNS in vivo, and in DC:TC cultures in vitro, which correlated with sparing of myelin and axons, together demonstrate a previously unknown immunomodulatory capacity for ER-β treatment. Notably, because ER-β is broadly expressed in the CNS on neurons, astrocytes, and oligodendrocytes, our findings do not preclude additional neuroprotective mechanisms as well. Nevertheless, our findings clearly support

the notion that ER-β ligand treatment should now be considered a potential strategy to attenuate DC function in the target organ of autoimmune demyelinating diseases. Female ER-β homozygous knockout mice were purchased from Taconic Farms (Germantown, NY, USA), and female WT C57BL/6 and B6.Cg-Tg (Thy1-YFP) C-X-C chemokine receptor type 7 (CXCR-7) 16Jrs/J mice were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). Animals were maintained under standard conditions in a 12-h dark/light cycle with access to food and water ad libitum. All procedures were done in accordance with the guidelines of the National Institutes of Health and the Chancellor’s

Animal Research Committee of the University of California, Los Angeles Office for the Protection of Research Subjects. Animals were subcutaneously injected with myelin oligodendrocyte glycoprotein (MOG), amino acids 35–55 (200 μg/animal, American Peptides) emulsified in complete Freund’s adjuvant and supplemented with Mycobacterium tuberculosis H37Ra (200 μg/animal, Difco Laboratories) over four draining inguinal and axillary LN sites in a volume of 0.1 mL/mouse. Animals were either treated with vehicle consisting of 10% molecular-grade ethanol (EM Sciences) and 90% Miglylol 812N liquid oil (Sasol North America) or the ER-β ligand, Diarylproprionitrile (Tocris Biosciences) diluted with vehicle at a dose of 8 mg/kg/day for seven days before immunization or adoptive transfer of in vitro stimulated lymphocytes.

It has been suggested that apoptosis of infected macrophages is one way in which the host deals with intracellular pathogens and that M. tuberculosis can inhibit this process. To assess the relevance of this process for

human disease, we compared the expression of multiple genes involved in the activation of the extrinsic (“death receptor initiated”) pathway of apoptosis BVD-523 mw in 29 tuberculosis patients, 70 tuberculosis contacts and 27 community controls from Ethiopia. We found that there is a strong upregulation of genes for factors that promote apoptosis in PBMC from individuals with active disease, including TNF-α and its receptors, Fas and FasL and pro-Caspase 8. The anti-apoptotic factor FLIP, however, was also upregulated. A possible explanation for this dichotomy was given by fractionation of PBMC using CD14, which suggests that macrophage/monocytes may regulate several key molecules differently from non-monocytic cells (especially TNF-α and its receptors, a finding confirmed by protein ELISA) potentially reducing the sensitivity to apoptotic death of monocyte/macrophages – the primary host cell for M. tuberculosis. This may represent an important survival strategy for the pathogen. Despite vaccination and drug treatment campaigns, tuberculosis (TB) causes an estimated 8–9 million new cases and mortality of 2–3 million deaths annually 1. The TB epidemic is largely

confined to developing countries, and is particularly serious in Sub-Saharan Africa 2, where it is fanned by the HIV epidemic. Despite the RXDX-106 in vivo high mortality, most infected people do not immediately develop active disease, but become latently infected – though they may later reactivate their disease, if they become immunocompromised 3. It is thought that perhaps as much

as a third of the world’s population is latently infected, 4 complicating control Thalidomide efforts by providing a reservoir from which new cases continually arise. Understanding immunity to Mycobacterium tuberculosis, so that more effective vaccines can be developed, is thus an international priority. The response to infection with M. tuberculosis is characterized by a strong inflammatory cell-mediated immune response, with elevated expression of both TNF-α 5–7 and IFN-γ 8–10. These two cytokines are essential for controlling mycobacterial infections 11–13 but in most cases, M. tuberculosis survives to establish a latent infection – which can rapidly reactivate if TNF-α production is blocked 14. The precise mechanisms involved in this process are still only poorly known. We and others have previously shown that a bias towards IL-4 expression is associated with elevated risk of disease 15 while a bias towards the IL-4 antagonist IL-4δ2, or towards IFN-γ, is associated with reduced pathology, a better prognosis after infection, recovery after treatment and with the ability to maintain the infection in a latent state 16–19. Thus, the immune response to M.

5A and B). Similarly, when BAFF activity was prevented by the addition of a specific BAFF neutralizing Ab to PBMC cultures, a reduction in the TLR7-stimulated IgM and IgG production was obtained (Supporting Information Fig. 3). A different picture was found when Ig release was measured upon TLR9 triggering in either monocyte-depleted PBMCs or whole PBMCs treated with anti-BAFF Ab. Indeed, an enhanced release

of both IgM and IgG was observed in response to TLR9 stimulation in the absence of monocytes while the neutralization of BAFF poorly affected Ig Cytoskeletal Signaling inhibitor production (Fig. 5A and B and Supporting Information Fig. 3, respectively). This result was not obvious and, at this stage, it is difficult to explain but it suggests that monocytes could be associated to a negative feedback loop on TLR9-driven B-cell differentiation while they positively act on the TLR7 responsiveness of Ig-producing Selleckchem Napabucasin B cells. Thus, we can envisage that changes in the basal and/or TLR-induced cytokine milieu of in vivo IFN-β-conditioned PBMCs could profoundly impact on Ig production from B cells in response to TLR7 or TLR9 stimulation. Collectively, these findings demonstrate that the cross-talk between monocytes and B cells is essential for the release of an effective humoral immune response in the context of

TLR7 stimulation affecting the maturation and differentiation status of B lymphocytes into Ig-secreting cells. Over the past decade, there has been growing understanding and acceptance of the pathological involvement

of B cells and humoral response in MS [1, 2]. The demonstration that peripheral B-cell depletion leads to a rapid decline in disease activity in MS is the strongest evidence of the central role of these cells in MS autoimmunity [9, 11]. However, the key question that still remains unsolved is when and how in the Ribonucleotide reductase life of an individual B cell does provide immunopathogenic support or arise as a disease-relevant cell type in MS. In this study, we investigated whether IFN-β targets B lymphocytes and modulates their functions contributing to the protective effects of this treatment. Only a few studies have thus far addressed this point and most have investigated the ability of highly purified B cells from MS patients to present antigens and subsequently regulate T-cell responses [28, 29]. In contrast, we studied whether IFN-β therapy would regulate the maturation and differentiation of B cells into Ig-secreting cells in response to TLR7 or TLR9 stimulation. Indeed, it has been shown that TLR triggering is necessary for extensive human naïve B-cell proliferation, isotypic switching, and production of Abs providing the third signal upon BCR cross-linking by antigen and interaction with T helper cells [30].

Detection of IL-17A-producing cells was determined by intracellular staining with anti-IL-17-PE (eBio17B7, eBioscience (Frankfurt, Germany)). Foxp3-expressing cells were detected by using the Foxp3 staining kit (anti-Foxp3-PE, FJK, FJK-16s, eBioscience). In some experiments, the amounts of IL-2 secreted by activated cells were measured by ELISA (BD), as described earlier 32. For the IRF-4 immunoblots, whole-cell lysates were prepared as described earlier 32. In brief, phosphatase inhibitors (0.2 mM sodium vanadate, 10 mM sodium fluoride) and 1× complete protease inhibitor (Roche Applied Science) were added into RIPA lysis buffer. Washed cell pellets were incubated on ice for 20 min in RIPA buffer and cell

debris was sedimented by centrifugation at 10 000×g for 10 min. Supernatants Dabrafenib chemical structure were used as cell lysates. The protein concentration was determined using the Micro BCA Protein Assay Kit (Pierce, Rockford, USA) and subsequently 20 μg of total protein were denaturated in 4× Laemmli Buffer and separated by 10% SDS-PAGE. Following SDS-PAGE, samples were transferred to nitrocellulose membrane

(Millipore(Schwalbach am Taunus, Germany)) at 100 V in transfer buffer. For the detection of IRF-4 protein, anti-IRF-4 (M-17, sc6059; Santa Cruz Biotechnology) revealed by donkey anti-goat IgG-HRP (Santa Cruz Biotechnology (Heidelberg, https://www.selleckchem.com/products/AZD2281(Olaparib).html Germany)) was used. As a loading control for protein samples, a monoclonal anti-mouse β-actin antibody (Sigma) was used. For statistical analysis, the two-tailed Student’s t-test was used. Guanylate cyclase 2C p-Values of <0.05 were considered as significant. The authors thank Anna Guralnik and Bärbel Casper for technical support and Hartmann Raifer for helpful discussions. This work was supported by the DFG (SFB TR22, GRK767 and SFB633) and Gemeinnützige Hertie-Stiftung. Conflict of interest: The authors declare no financial or commercial conflict of interest. See accompanying Commentary: http://dx.doi.org/10.1002/eji.201040372 "
“Compounds targeting the chemokine receptor CCR5 have recently been approved for treatment of human immunodeficiency virus (HIV) infection.

Given the central role of CCR5 in inflammation and recruitment of antigen-presenting cells (APC), it is important to investigate the immunological consequences of pharmacological inhibition of CCR5. We evaluated the in vitro effect of different concentrations of CCR5 antagonist maraviroc (MVC) on cell migration of monocytes, macrophages (MO) and monocyte-derived dendritic cells (MDC) towards peptide formyl-methionyl-leucyl-phenylalanine (fMLP) and chemokines regulated upon activation normal T cell expressed and secreted (RANTES) and CCL4/macrophage inflammatory protein-1 (MIP-1β) and CCL2/monocyte chemotactic protein-1 (MCP-1). Results of flow cytometric analysis showed that monocytes treated in vitro with MVC exhibited a significant dose-dependent reduction of chemotaxis towards MIP-1β and MCP-1.