In most previous FHF outbreaks, there were usually one or a few primary introductions of infection to humans, after which spread occurred

by human to human transmission [8, 9]. There were however, multiple, short, independent chains of human-to-human Veliparib chemical structure transmission in the 1998 MVD outbreak in the DRC, at least nine genetic lineages of the virus being involved, and multiple independent chains of transmission from infected non-human primates in the 2001 EVD outbreaks in Gabon and the RC [9, 10]. Some outbreaks of EVD are thought to be associated with hunting and processing of bush meat, whereas MVD outbreaks have often been associated with entry into caves or working/decommissioned mines [9-11]. Primary infection is followed by human to human transmission via contact Doramapimod cell line with body fluids of infected individuals [8, 12]. There is usually a delay between the initial cases and the diagnosis of FHF. This is attributable to the remoteness of most affected areas, their ill-equipped medical facilities and the fact that signs and symptoms of FHF are mainly non-specific, leading to FHF being misdiagnosed as other more frequent infections that are endemic to the area [8,

13]. While it is possible that some cases have occurred without virus-specific laboratory diagnosis, outbreaks of FHF have been increasingly reported [14-16]. This review paper looks at recent FHF outbreaks in Africa and discusses the potential risk of such outbreaks in previously unaffected areas. The genus Marburgvirus has one species, Marburg marburgvirus, with two viruses, namely MARV and RAVV [17]. Egyptian fruit bats (Rousettus aegyptiacus) were recently found to be the most likely natural reservoir host for marburgviruses [18]. Many outbreaks have been associated with entry into working/decommissioned mines or caves [2, 11, 19] in which the bats stay. The most recent MVD outbreaks occurred in Uganda

in 2012 (Table 2). MARV infections in Egyptian fruit bats have been found to have seasonal fluctuations, with biannual peaks that correspond to infections in humans [18]. The 2012 outbreak occurred during one of the peaks of MARV infections in bats. The full length genome sequences from this outbreak showed 99.3% sequence identity to MARV from bats captured in 2008 and 2009 in a nearby cave [20]. In 2007 Urease there were two independent outbreaks in Uganda, occurring in miners who had had close contact with bats. In June 2007, three people were infected and one died, whereas in the later outbreak there was only one case and no mortality [11]. There was 21% sequence variation between the full-length RNA genomes of these viruses, the earlier one being closely related to historical MARV sequences and the later one more closely related to RAVV, which was first isolated in Kenya in 1987. Both MARV- and RAVV-related sequences were also found in fruit bats (R. aegyptiacus) in the same area [21]. The 2004–2005 MVD outbreak in Angola was the first report of MVD outside East Africa.

22,23 In addition, miR-146a may also negatively regulate the interferon-γ (IFN-γ) pathway, indirectly contributing to the ‘interferon signature’ of SLE.24 Taken together, our result is consistent with the

hypothesis that miRNA plays a functionally important role in the pathogenesis of LN. There are a number of inadequacies of our study. First, the choice of miRNA target was limited. The panel of miRNA was selected because they were reported to be involved in the pathogenesis of SLE,9–14 and our group had previously reported the serum and urinary expression of miR-146a and miR-155 in LN patients.12 Nonetheless, our study represents a very limited examination of the large number of human miRNAs that exist and which might be dysregulated Aloxistatin clinical trial in lupus nephritis. On one hand, it is possible that the findings of our present study are the consequence

of renal disease rather than playing a role in the pathogenesis and an examination of miRNA expression in renal selleck kinase inhibitor biopsy from patients with non-lupus renal diseases may be necessary to discern this possibility. On the other, it is also probable that other miRNA targets may also be involved. For example, a recent report from Luo et al.25 observed a tendency of reduced miR-146a expression in lupus patients, while Stagakis et al.26 found that miR-181a, miR-21 and miR-126 may be involved in the pathogenesis of lupus nephritis. In theory, the use of hypothesis-free Farnesyltransferase expression profiling (for example, microarray) may allow a complete evaluation of all possible miRNA targets. However, the amount of miRNA that could be harvested from micro-dissection specimen is often limited and usually not sufficient for microarray analysis. In the

future, newer technologies may be increasingly able to profile a much broader spectrum of miRNAs from smaller quantities of tissue RNA, while in situ hybridization examination of miRNA expression may provide substantial insight to the understanding of the role of miRNA in lupus nephritis. Another approach for future research would be to focus on miRNAs specifically expressed in glomeruli or tubulointerstitium. Another major limitation is that the present study is cross-sectional and it is possible that miRNA expression levels may change with disease progression or in response to immunosuppressive therapy. Future studies are needed to evaluate the serial change in the intra-renal expression of miRNAs. It is also possible that the control tissues of our present study, which came from nephrectomy specimens, might have been handled and processed in a slightly different manner, resulting in the observed differences from the lupus specimens.

9 ng/mL for IL-2 and 31.25 ng/mL for IL-10. NO2− determination was carried out by the Griess assay as described 40 with some modifications. Briefly, 100 μL of each sample was added to each well of a 96-well plate

in duplicate, 50 μL of 1% sulfanilamide (Sigma) in 2.5% H3PO4 was added and incubated for 5 min, 50 μL of 0.1% naphtylenediamine dihydrochloride (Sigma) was added and incubated for 10 min (room temperature, in the dark); absorbance was read at 540 nm. Standard curves were prepared with sodium nitrite and the detection limit was 1.56 μM. Statistical differences between groups were determined by the unpaired two-tailed Student t-test or One-Way ANOVA with Dunnett’s or Bonferroni’s Multiple Comparison tests using the PRISM software (GraphPad). This work was supported by grants IN-200608 and IN-209111 from PAPIIT (DGAPA, UNAM, Mexico) and by grants 79775, Wnt inhibitor 102399 and 102984 from CONACYT (Mexico). The authors are grateful to M. V. Z. Georgina Díaz and M. V. Z. Jorge Omar García for their expert advice and help in the care of the animals and Katharine A. Muirhead for helpful advices on cell tracking dyes. E. P. T.

Ibrutinib is recipient of a PhD fellowship from CONACYT (Registro 199991). This work was performed in partial fulfillment of the requirements for the PhD Program of Doctorado en Ciencias Biomédicas of E. P. T. at the Universidad Nacional Autónoma de México. Conflict of interest: The authors have declared no financial or commercial conflict of interest. “
“IgG4 and IgE are immunoglobulin isotypes which are mediated by the same Th2-mediated mechanism. The postulated pathogenic

and protective function of IgE or IgG4, respectively, in allergic disease is opposite in parasitic infection. The possible role of IgG4 against recombinant major allergens on the appearance of different forms of Anisakis simplex-associated selleck products allergic disease was studied. Gastro-allergic anisakiasis (GAA) and Anisakis-sensitization-associated chronic urticaria (CU+) were compared for specific IgE, IgG4 and the respective recognition of Ani s 1 and Ani s 7. Gastro-allergic anisakiasis showed higher IgE and IgG4 levels against crude extract and both recombinant allergens. Whereas IgE recognition of Ani s 7 did not differ and supports both clinical entities to be associated with previous acute parasitism, the IgE recognition rates of Ani s 1 and IgG4 recognition of both Ani s 1 and Ani s 7 were higher in GAA. IgG4 levels were associated with IgE, but also with age, time to last parasitic episode and frequency of fish intake. Logistic regression analysis showed that the presence of specific IgG4 against Ani s 7 was an independent marker associated with GAA. In the diagnosis of Anisakis-associated allergic disease phenotypes (GAA versus CU+), measurement of specific IgG4 against recombinant allergens could be useful. Further, evaluation of specific IgE and IgG4 facilitates more insight into the protective versus pathogenic potential of IgE and IgG4.

tuberculosis-infected guinea pigs or animals with experimental tuberculous pleuritis enhanced splenic granuloma organization and inflammatory processes [20–25]. This is the first study that demonstrates that rgpTNF-α exerts immunomodulatory effects when injected after BCG vaccination in guinea pigs. The dose of TNF-α was selected on the basis of previous studies in mice [13,16,31]. TNF ZD1839 supplier treatment was not associated with overt toxicity, as the guinea pigs did not display weight loss, morbidity or mortality. TNF-α is known

to mediate a number of immunological functions after M. tuberculosis infection including cell recruitment, induction of chemokine and cytokine secretion, macrophage activation and apoptosis, in addition to synergizing with IFN-γ in the formation and maintenance of granuloma [19,32–34]. Injection of guinea pigs with rgpTNF-α induced an increase in the PPD skin test response (Fig. 1a), suggesting that it may enhance leucocyte recruitment and/or other aspects of the dermal inflammatory responses at the site of antigen challenge in the M. bovis BCG-vaccinated animals. TNF-α treatment also resulted in an increase in the Pexidartinib clinical trial infiltration of mononuclear cells in the lymph nodes draining the vaccination site (Fig. 6), as well as an increase in the proportions of CD3+ T cells (Fig. 3a). An increase in CD3+

T cells after TNF-α treatment was not accompanied by an increase in the number of CD4 or CD8+ T cell subsets. One explanation for this result could be that while all α and β T cell receptor-positive T cells express CD3 antigen on their surface, cells other than CD3+ T cells, such as macrophages or dendritic cells, are also known to express CD4 or CD8 markers [35]. Thus, a concomitant change in the CD4 or CD8+ T cells may not be evident in these

experiments, and in future this can be addressed by the double staining of cells against CD3 and CD4 or CD8 T cell phenotypic markers. In addition, Protein tyrosine phosphatase antigen-specific T cell proliferation to PPD was enhanced in the lymph nodes of guinea pigs treated with rgpTNF-α, while Con-A-induced proliferation of T cells remained unaltered in these animals (Fig. 2c). The results from these in vivo studies are consistent with the in vitro observations reported earlier from our laboratory, that treatment with rgpTNF-α of spleen cells from BCG-vaccinated guinea pigs enhanced the T cell proliferation to PPD and not ConA [21]. The differential effect of TNF-α on PPD or ConA-induced T cell proliferation may be attributed to the differential contributions of co-stimulation by antigen-presenting cells (APC), as reported by others [36,37]. From our study, as well as from others, it is clear that TNF-α causes further proliferation of T cells but TNF blockade enhances both Th1 (IFN-γ and IL-12p40) and Th2 (IL-10) cytokine responses in mice with chronic tuberculosis infection [13,21].

11 When exposed to a solution containing more active monovalent and divalent cations – like potassium (K+), calcium (Ca++) or magnesium (Mg++) – it will preferentially release Na+ and H+ into solution and, in exchange, bind the other ions. In the early 1960s, NASA sought to purify waste water and human effluent to minimize water carriage in rocket payloads and to act as a renewable water source for manned space travel. Sorbents soon emerged as an ideal way to remove a wide range of human effluent waste substances from solution. They proved remarkably effective and efficient water purifiers. Sorbents were first adapted to the purification of blood by Reynolds, who used zirconium phosphate as an adsorbent to

remove ammonium from a test solution. RG-7388 Sorbent chemistry was soon applied to effluent dialysate from an artificial kidney circuit to test dialysate effluent reuse potentials. The REDY system – an acronym for REcirculation of DialYsate – then emerged.3,4 The REDY used a disposable, one-use sorbent cartridge. This contained activated

Pifithrin-�� charcoal, urease and zirconium phosphate that, when used in series, purified the dialysate effluent and permitted dialysate regeneration. Only 6 L of tap water was required. This compared with as much as several hundred L/treatment (depending upon R/O plant efficiency) required by a conventional single pass system. Post-cartridge effluent water purity reached near ultra-pure quality despite the absence of a continuous water source. A drain was not needed. The only anchoring connection was a standard circuit power source. The serial REDY models of the 1970–1980s were the first truly portable dialysis systems and were widely used throughout Australian hospitals, especially for bedside dialysis in acute renal failure. Importantly, they were also deployed

in Australian homes for home-based haemodialysis. This was a likely factor at that time in the coincident success of Australian home haemodialysis. In both the REDY system and the more recent clinical prototype sorbent system, the Allient,12–14‘used’ or ‘effluent’ post-dialyser dialysate containing the usual solute products of dialysis passed through a multilayered column of adsorptive materials. These adsorbents were designed to trap Clomifene or ‘adsorb’ these solutes – and other substances including endotoxin and bacteria – and remove them from the dialysate. In addition, excess dialysed ions – K+, Ca++, Mg++ and phosphate (PO4≡) – were exchanged for benign or less toxic ions like Na+, H+, bicarbonate (HCO3-) and acetate.* The ‘reconstituted’ fluid emerged from the sorbent cartridge as ‘purified’ water containing Na+, HCO3- and a small amount of acetate. A final step was required – the re-addition of a known concentration of K+, Ca++, Mg++– to fully reconstitute the dialysate before its’ representation at the dialyser as an ‘infusate’. The entire sorbent process has been well described by Ash.

At present in Darwin, Australia, patients on substantial immunosuppressive therapy, such as adults on

PLX-4720 molecular weight 40 mg/day or more of prednisolone or equivalent corticosteroid therapy for 4 weeks or more and those on severe chemotherapy, are recommended for TMP + SMX 160 mg/800 mg (one double strength tablet) daily during the monsoonal wet season. While the value of recommendations for preventing exposure to B. pseudomallei has not been formally evaluated, such recommendations are seen as increasingly important with the escalating numbers of patients in endemic areas with diabetes, chronic renal disease and heavy immunosuppressive therapy. Most important is limiting exposure to wet season soils and surface water in these patients by avoiding gardening or other risk activities during the wet season, or as a minimum wearing protective foot-wear and protective gear during such activities. With the increasing concern of potential inhalation of B. pseudomallei, high-risk patients are now being told to stay indoors during severe

weather events where BIBW2992 cell line winds and rain may result in B. pseudomallei contaminated droplets or aerosols.[55] Successful management of melioidosis requires a high index of suspicion for early diagnosis, adequate prognostic evaluation of its severity and specific anti-microbial therapy for a prolonged duration to avoid mortality. Melioidosis could potentially be avoided with adequate preventive measures. Hence, the overall need for awareness of this potentially fatal infectious disease among physicians managing at-risk patients cannot be underestimated. None declared. “
“Increasing evidence implicates Tenofovir in vitro psychosocial factors including depression, anxiety, perceived social support

and health-related quality of life in the pathophysiology of various chronic diseases. Research examining the psychosocial aspects of kidney disease has focussed predominantly on depressive disorders in dialysis patients where they are independently associated with increased risk of mortality and poor health-related quality of life. In contrast, studies examining the influence of psychosocial factors in people with chronic kidney disease (CKD) prior to the initiation of renal replacement therapy are sparse. Limited data indicate that clinical depression and depressive symptoms are common and may independently predict progression to dialysis, hospitalization and death. In contrast, the influence of anxiety disorders, lower perceived social support and impaired health-related quality of life on the clinical course of CKD have received little attention. Large-scale prospective cohort studies are needed to clarify the burden and prognostic impact of these factors in this vulnerable population. Given the escalating burden of CKD worldwide examining the role of these potentially modifiable risk factors is crucial.

Data were analyzed with FlowJo software (Tree Star, Ashland, OR, USA). BALF cells were placed on glass slides by cytospin (Cytospin 3, SHANDON, Waltham, MA, USA). After

air-drying for 20 min, slides were fixed with 1% PFA/PBS for 10 min. After washing with 0.1% Tween-20/PBS, slides were blocked with 3% BSA/0.1% Tween-20/PBS for 1 h at room temperature, then incubated with polyclonal rabbit anti-mouse arginase 1 Ab (Santa Cruz) and Rat anti-mouse F4/80 Ab (AbD Serotec, Oxford, UK) at 4°C overnight, followed by incubation R788 datasheet with Alexa Fluor 594-conjugated anti-rabbit Ab (Molecular Probes) and Alexa Fluor 488-conjugated anti-rat Ab (Molecular Probes, Japan, K.K. Tokyo, Japan), respectively. Fluorescent images were observed by confocal microscopy (Bio-Rad Radiance 2100, Bio-Rad). We observed more than 300 F4/80+ cells and then calculated the percentage of arginase 1+ cells in the F4/80+ cells. BM cells obtained from naïve female C57BL/6 mice were used for in vitro assays. BM cells were harvested from femurs and tibias, treated with RBC lysis solution, and then sorted for CD117+ cells using a Metformin mw c-kit isolation kit (Miltenyi Biotec, Bergisch Gladbach, Germany) according to the manufacturer’s

protocol. The purity of CD117+ cells was>60% in our experiments. Harvested cells were cultured with Gal-9 (3 and 30 nM) in the presence or absence of T. asahii for 5 days. Very stringent gating Florfenicol conditions were used for sorting experiments (FACSAria, Becton Dickinson), with purity checked by

flow cytometry: CD11b+Ly-6C+Ly-6G− cells and CD11b+Ly-6C−Ly-6G+ cells were>95%. Harvested cell pellets were dissolved in SDS lysis buffer, boiled, fractionated on an SDS-polyacrylamide gel, and transferred to a nitrocellulose membrane. After blocking with PBS plus 0.1% Tween-20 containing 5% skim milk for 1 h at room temperature, the membrane was incubated with antibodies against NOS2 (Abcam, Cambridge, MA, USA) and arginase1 (Santa Cruz, CA, USA) overnight at 4°C. After washing with PBS plus 0.1% Tween-20, the membrane was incubated with anti-HRP-linked Ab for 1 h at room temperature and visualized with Western lightning chemiluminescence reagent (PerkinElmer, Waltham, MA, USA) according to the manufacturer’s protocol. Extracts from mouse liver and whole lung tissue were used as positive controls for NOS2 and arginase 1, respectively. T-cell proliferation was evaluated using splenic CD4+ T cells and BALF cells obtained from PBS-treated mice or Gal-9-treated mice.

Altogether, these studies demonstrated that, in addition to the Volasertib cost major population of large monocytes, smaller monocytes with different characteristics such as reduced superoxide production capacity and peroxidase activity are present in the blood [3-6]. In humans, small monocytes can be distinguished from classical monocytes on the basis of their expression of the CD16/Fc-γRIII receptor [8]. Since small CD14+ CD16+ monocytes produce less IL-10 and more inflammatory molecules, such as IL-1β and TNF, in response to microbial stimuli compared with that produced by regular-sized CD16− monocytes, CD14+ and CD16+ monocytes

are often referred to as “inflammatory monocytes” [6, 9, 10]. Further fuelling this reputation is the fact that circulating CD16+ monocytes are reported to increase during inflammation in a number of diseases such as rheumatoid arthritis, atherosclerosis, sepsis, and AIDS, among others, and that these cells actually contribute to inflammation in different contexts (e.g., obesity) [1, 11, 12]. A better understanding of monocyte differentiation programs and consequent biological functions in different microenvironments, along with developing strategies to target and manipulate these monocytes in vivo, constitute pressing issues in modern immunopathology studies. Tuberculosis (TB) represents an infectious disease that still remains in the shadow cast by a defective

APC compartment. Its etiological agent, AP24534 cell line Mycobacterium tuberculosis, mainly infects the respiratory system where it can persist for years — and up to decades — due to a number of strategies that M. tuberculosis has evolved to circumvent or impair immune recognition and reaction [13, 14]. Chief among these strategies is the well-known ability of M. tuberculosis to impair DC differentiation, maturation, circulation, and APC functions, as compared with that of other microbial stimuli such as LPS from Gram-negative bacteria [15-20]. Indeed, deciphering how M. tuberculosis deters DC functions in vivo holds promise in terms of therapeutic application. In this context, Balboa et al. [21] now report in this issue of the

European Journal of Immunology that inflammatory CD16+ monocytes, the proportion of which is known to increase in the blood Thymidine kinase of patients with TB, are refractory to DC differentiation as measured by CD1a and DC-SIGN expression (Fig. 1). The novel information provided by this study is i) CD16+ monocytes from TB patients are intrinsically refractory to DC differentiation upon treatment with GM-CSF and IL-4, and do not “”transmit”" this property to CD16− monocytes in vitro, ii) this property is due to hyperactivation of the p38 MAP kinase, and iii) the proportion of CD16+ monocytes directly correlates with that of altered DCs, as defined by the DC-SIGNlowCD86high profile on the DCs in the blood of TB patients. The strength of the study by Balboa et al. [21] stems from the use of monocytes freshly isolated from TB patients and healthy subjects.

Fresh green tea extract.  Whole green tea (Camelia sinensis L) extract (Topix Pharmaceuticals, West Babylon, NY, USA) was suspended in RPMI-1640 (Sigma, St. Louis, MO, USA) at a concentration of 1 g/100 ml and further diluted for the experiments. The extract contained a 90% polyphenol isolate from whole leaf, with 80% catechins; EGCG composed 70% of catechins. GTE was freshly prepared prior to each experiment, and leftover solution was stored BMS-777607 at 4°C. Epigallocatechin Gallate.  Purified EGCG (>95% purity; Sigma-Aldrich, St. Louis, MO, USA) was suspended in RPMI-1640

(Sigma) at a concentration of 1 g/100 ml and further diluted to concentrations of 50% because of the 50% content of EGCG in the GTE used. The GTE contained 90% polyphenols, and 80% of the polyphenols are catechins. 70% of the catechins are EGCG, which approximates to 50% of the GTE is EGCG. Based on the above, the EGCG concentration in culture was 50% of the GTE concentration. Cell Cultures.  Human PBMC (1.5 × 106 cells/ml) were separated on a Ficoll-Paque (Pharmacia, Piscataway, NJ, USA) gradient (density 1.077) and washed twice in RPMI-1640 medium (Gibco/BRL, Grand Island, NY, USA) and counted. Cells Everolimus clinical trial were then cultured in complete RPMI medium (c-RPMI) containing L-glutamine (2 mm) (Sigma), penicillin (100 Units/ml)

(Sigma), streptomycin (100 μg/ml) (Sigma) and N-2-hydroxyethylpiperazine-N’-2-ethanesulfonic acid buffer (HEPES) (25 mm) Reverse transcriptase (Sigma) and supplemented with heat-inactivated foetal calf serum (FCS) (10%) (Gibco), ± recombinant human interleukin-4 (IL-4) (100 ng/ml) (R&D), ± mouse anti-human monoclonal (mAb) CD40 (1 μg/ml) (BD Pharmingen Transduction Labs, San Diego, CA, USA), ± varying concentrations of GTE (1–100 ng/ml) (Topix Pharmaceuticals, West Babylon, NY, USA) or EGCG (0.5–50 ng/ml) (Sigma). In some experiments,

cat pelt antigen (1 AU/ml) (Alk-Abelló, Hørsholm, Denmark) was added to cultures to assess for differences between allergen- and non-specific IgE responses; cat pelt was chosen because all three subjects had positive SPT to cat pelt. Control cultures included anti-CD40 and rhIL-4 without cat pelt antigen. The cells were then cultured for 10 days at 37°C in a humidified atmosphere of 4% CO2 in air, after which supernatants were collected and frozen (−20°C), and then assayed for IgE production. (ELISA, BioQuant, San Diego CA, USA). Cell viability.  Cell viability was >90% as judged by trypan blue (Gibco) exclusion on day 10 in all cultures (±GTE). Quantification of IgE production.  In vitro quantitative determination of IgE content in cell culture supernatants was performed using a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) (IgE ELISA Test Kits, BIOQUANT). All ELISAs were performed according to the manufacturer’s recommended procedure. Specimens were analysed in triplicate and a standard curve was derived from known concentrations of IgE.

This work was in part supported by National Institutes of Health

grants T32 HL007749 (CMT), U19 AI090871 (GBH and VBY), P30 DK034933 (GBH and VBY) and RO1 DK084058 (DTR). AASA and GBH conceived, designed and interpreted the experiments; CMT, JRED, DTR and VBY contributed to the design and interpretation. AASA, CMT, AJM, NRF and HMT performed the experiments. AASA, JRED, DTR and GBH analysed the data. AASA and GBH wrote the manuscript and all the other authors provided comment and advice on www.selleckchem.com/products/azd-1208.html the manuscript. Vincent B. Young is on the advisory board of ViroPharma in relation to developing non-toxigenic C. difficile for the management of C. difficile infection. The other authors declare no conflict of interest. “
“Borrelia

www.selleckchem.com/products/poziotinib-hm781-36b.html burgdorferi spirochetes cause Lyme disease, which can result in severe clinical symptoms such as multiple joint inflammation and neurological disorders. IFN-γ and IL-17 have been suggested to play an important role in the host defense against Borrelia, and in the immunopathology of Lyme disease. The caspase-1-dependent cytokine IL-1β has been linked to the generation of IL-17-producing T cells, whereas caspase-1-mediated IL-18 is crucial for IFN-γ production. In this study, we show by using knockout mice the role of inflammasome-activated caspase-1 in the regulation of cytokine responses by B. burgdorferi. Caspase-1-deficient cells showed significantly less IFN-γ and IL-17 production after Borrelia stimulation. A lack of IL-1β was responsible for the defective Loperamide IL-17 production, whereas IL-18 was crucial for the IFN-γ production. Caspase-1-dependent IL-33 played no role in the Borrelia-induced production of IL-1β, IFN-γ or IL-17. In conclusion, we describe for the first time the role of the inflammasome-dependent caspase-1 activation of cytokines in the regulation of IL-17 production induced by Borrelia spp. As IL-17 has been implicated in the pathogenesis of chronic Lyme disease, these data suggest that caspase-1 targeting may represent a new immunomodulatory strategy for the treatment of complications of late stage Lyme

disease. Lyme disease is caused by spirochetes of the genus Borrelia, of which Borrelia burgdorferi sensu stricto is causing disease mainly in the United States, and Borrelia afzelii and Borrelia garinii mainly cause disease in Europe and Asia 1, 2. Clinical Lyme disease can be divided into early localized infection that is often characterized by skin manifestations, and in either the early or late disseminated stage of the disease joint and skin inflammation, as well as neurologic disorders can be seen 3. Various Borrelia strains appear to cause different clinical symptoms in Europe. B. burgdorferi sensu stricto is the main cause of Lyme arthritis, B. garinii most often induces neurologic manifestations, while B. afzelii is mainly responsible for skin disorders 4, 5.