γ-Cystathionase activity was equally elevated in predialysis period and in peritoneal dialysis patients, which means that chronic kidney disease pathology is accompanied by an increased expression of this enzymatic activity in erythrocytes. Erythrocytic rhodanese activity was unchanged and stayed at the control level in both groups. Protein carbonylation rate was equally enhanced in both patient groups, which indicated acceleration of oxidative processes and inability of continuous ambulatory peritoneal

dialysis to correct these changes in erythrocytes. Conclusion:  The CAPD as a replacement therapy helps to preserve thiol levels and anaerobic sulfur metabolism in erythrocytes. “
“Date written: July 2008 Final submission: February 2009 No recommendations possible based on Level I or II evidence (Suggestions are based on Level III and IV evidence) A combination of waist circumference and body mass index (BMI) is recommended Cisplatin order for the clinical assessment of overweight and obesity.1 Consideration of differential risk according to ethnicity should be undertaken. 1 Survey Australian and New Zealand renal units to determine current practice in terms of acceptance of obese donors. The aim of this guideline is to examine the consequences of

obesity on short- and long-term donor outcomes following nephrectomy EPZ-6438 molecular weight for purposes of living donor transplantation. Due to the increasing prevalence of obesity in the general population, an increasing percentage of donors coming forward for assessment are overweight

and obese. They are often young or middle aged, frequently with no current medical issues and have a projected life expectancy of many decades. The assessment involves consideration of future risk, which is often difficult to Celecoxib quantitate versus the more immediate and tangible benefit to the recipient. Areas of concern relating to obesity are as follows: it is a risk factor for perioperative morbidity Therefore, the consideration of the impact of nephrectomy in this group is a significant issue for which there is a paucity of long-term data from which to draw firm conclusions. A number of techniques are available for the assessment of adiposity. BMI (kg/m2) is easy to use and reproducible and has been consistently associated with increased risk of mortality, development of CVD and diabetes. However, BMI does not take into account variability of fat distribution or proportion of weight related to muscle or changes associated with aging. Excess intra-abdominal fat is associated with a greater CVD risk than overall adiposity. Alternative measurements of waist circumference and waist-to-hip ratio (WHR) have been proposed as alternatives to BMI and have been shown to be good simple measures of intra-abdominal fat mass and have stronger associations with hypertension and other CVD risk factors.

Thereafter, 100 μL of rabbit anti-goat IgG–HRP conjugate (1 : 3000 dilutions) was added. The plate was kept at room temperature for 90 min. The unbound conjugate was removed, and the wells were washed as before. Freshly prepared OPD (100 μL/well) was added, and the reaction was stopped after 5 min by adding 100 μL of 2·5 m H2SO4. The absorbance was measured at 490 nm in a Bio-Rad Model 680 microplate reader. The effect of H.c-C3BP on complement activity was measured by determining the lysis of sensitized sheep erythrocytes and formation of membrane attack complex (MAC). The erythrocyte lysis was determined essentially as described earlier [17] by measuring the release of haemoglobin at 415 nm from

ruptured erythrocytes due to complement selleck products action. In brief, sheep blood was collected in acid citrate and centrifuged at 400 g for 10 min (Remi

R8C, Remi Sales and Engineering Ltd., Mumbai, India). The plasma and buffy coat layer were discarded, and the packed RBCs were washed three times with normal saline. One volume of saline-washed RBC was mixed with one volume of 1 : 250 diluted decomplemented (at 56°C for 30 min) rabbit anti-sheep RBC antiserum (a kind gift from Dr. Tapas Goswami, Immunology Section, IVRI, Izatnagar) and incubated at 37°C for 30 min. The sensitized cells were washed three times with normal saline, with centrifugation at 400 g for 10 min. After the final wash, 2% cell suspension was prepared with saline containing 1 mm CaCl2. In initial experiments, 25 μL of normal rabbit serum gave appreciable cell lysis and was chosen for the assay. 3-Methyladenine The sensitized cells (100 μL) were incubated with 25 μL Ponatinib mw rabbit

serum in a total volume of 200 μL prepared with saline–calcium for an hour and further at 4°C for at least 4 h. For assessing the effect of H.c-C3BP, varying concentrations of protein were added to rabbit serum in saline–calcium and incubated at 4°C for an hour, followed by the addition of sensitized cells and further incubation. Control wells in triplicate with no serum, no protein, but 100 μL of saline–calcium and cells were included as negative control. Positive control wells had 100 μL of distilled water and cells. After incubation, 150 μL of the supernatant from each well was carefully aspirated and transferred to wells of a flat-bottomed microtitre plate, and the optical absorbance was measured at 415 nm. The effect of H.c-C3BP on complement C3 activation (MAC formation) was studied with modifications of earlier method [18]. The wells of a microtitre plate were coated with 100 μL of 10 μg/mL LPS in carbonate–bicarbonate buffer (100 mm, pH 9·6) and incubated at 4°C overnight. After washings, 100 μL of denatured gelatin in PBS was added and kept at room temperature for 90 min. After washings, 100 μL of fresh goat serum (1%) diluted in 10 mm Tris (pH 7·4) and 120 mm NaCl containing varying concentrations of H.c-C3BP (3·125–12·5 μg/mL) was added. The serum–H.

7a,b). Ki67 staining was largely absent in wild-type mucosal tissue following DSS treatment and coincided with the extensive destruction and loss of tissue architecture (Fig. 3). In contrast, widespread and strong Ki67 staining was found throughout the crypts of colonic tissue taken from DSS-treated Bcl-3−/− mice, indicating significantly enhanced proliferation of Bcl-3−/−

epithelial cells following treatment (Fig. 7a). Immunofluorescence microscopy analysis of Bcl-3 protein in tissue sections was unsuccessful using commercially available antibodies; however, previous studies have demonstrated Bcl-3 mRNA expression in intestinal epithelial cells [25, 26]. Taken together, these data suggest that Bcl-3−/− mice develop less severe clinical and histopathological

colitis due to an increase in epithelial proliferation, which leads to regeneration Natural Product Library purchase of the damaged epithelium. Our data also demonstrate that this regeneration occurs despite the presence of ongoing inflammation in the colonic mucosa. In this study we investigated the expression of Bcl-3 in human IBD and also the role of Bcl-3 in DSS-induced colitis in the mouse. We found that Bcl-3−/− mice develop less severe colitis compared to littermate control wild-type mice. These findings were unexpected, given the previously described role of Bcl-3 as a negative regulator of inflammatory gene expression check details [16] and the recent identification of reduced Bcl-3 expression as potential risk factors for CD [17]. However, the resistance of Bcl-3−/− mice to experimentally induced colitis correlates with our analysis of Bcl-3 expression in the colon of IBD patients, which was significantly increased when compared to healthy individuals. It is possible that the identified SNPs may lead to increased Bcl-3 expression rather than

decreased expression as predicted. Thus, our findings suggest that increased expression of Bcl-3 rather than reduced expression may be a potential risk factor for IBD. Our study also identifies a novel role for Bcl-3 in regulating intestinal selleck chemical epithelial cell proliferation during DSS-induced colitis. Analysis of cytokine expression during DSS-induced colitis in Bcl-3−/− mice revealed a robust inflammatory response following DSS treatment characterized by significantly elevated levels of proinflammatory cytokines TNF-α, IL-6 and IL-1β. The levels of these cytokines was similar to wild-type mice, indicating that Bcl-3 does not act as a negative regulator of TNF-α, IL-6 and IL-1β expression in the context of DSS-induced colonic inflammation. Histological analysis supported this observation further, as significant oedema and leucocyte infiltration were present in Bcl-3−/− colonic tissue sections and to a similar degree to that seen in wild-type mice.

1 mmol/L (2.1–7.1 mmol/L), potassium of 4.3 mmol/L (3.5–5.1 mmol/L),

bicarbonate of 7 mmol/L (22–32 mmol/L), C-reactive protein (CRP) of 162 mg/L (0–5 mg/L), a mild thrombocytopenia to 67 × 109/L (140–400 × 109) and neutrophilia to 15.9 × 109/L (2–8 × 109/L). Urinalysis showed proteinuria to 10 g/L and erythrocyturia (500 × 106/L). A glomerulonephritis screen was unremarkable except for minor elevations in Kappa free light chains to 46 mg/L (3–19 mg/L), Lambda free light chains to 31 mg/L (6–26 mg/L) Tanespimycin and serum protein electrophoresis revealed total protein depletion to 51 g/L (60–83 g/L) and albumin to 31 g/L (35–50 g/L). Remarkably, Lactate Dehydrogenase (LDH) rose from 304 U/L (150–280 U/L) at presentation to a maximum of 1360 U/L 2 days later, decreasing back to 564 U/L prior to discharge. Coagulation, haemolysis and infectious screens were negative (Blood Dabrafenib supplier cultures, HIV, Hepatitis B and C, Influenza A and B, Parainfluenza 1, 2 and 3, Human Metapneumovirus, Respiratory Syncitial virus, Adenovirus, Q fever, Leptospiria, Cytolomegalovirus, Ebstein Barr Virus). Renal biopsy revealed severe acute tubular necrosis (ATN) (Fig. 1). Histopathology reporting commented on the glomeruli as having ‘a mild increased in mesangial matrix but no hypercellularity.

Capillary loops appear normal in H/E and special stains. There are no features of thrombotic microangiopathy’. Furthermore there was no evidence of fibrinoid necrosis or pathological evidence of haemolytic uraemic syndrome. Uniquely this case is notable for both severity of clinical

and histological features of ATN. It presented dramatically with significant loin pain and an unexpectedly high rise in LDH. Westhuyzen et al. demonstrated that early LDH rise helps to predict ATN,[1] it was disproportionate in our case. Despite the histopathological changes of ATN being described as inconsistent and often subtle or mild,[2] the severity of ATN in this biopsy was marked. ADAM7 Often, morphological changes of ATN do not correlate well clinically.[3] In our case, histological severity was reflected in the profound clinical presentation. We report here a case of ATN with unusual presenting symptoms and clinically severe features. Our case was notable for the marked disproportionate rise in LDH at presentation, presence of severe loin pain and correlation of severe histological changes with profound clinical picture. “
“This review evaluates the benefits and harms of antiviral medications as prophylaxis after solid organ transplant (kidney, heart, liver, lung, pancreas) to prevent CMV disease. This includes prophylaxis with antiviral medications compared with placebo or no treatment, the comparative efficacy and safety of different antiviral medications and of different durations of the same antiviral agent.

These mechanisms are commonly interpreted in the context of avoiding chronic inflammation and limiting responses against omnipresent antigens (i.e. self-peptides) [124], but could also be mechanisms by which Th cell judges their combined success in fighting infections – including those induced by cytokine-expressing pathogens. Another possibility for evaluating success-driven

feedback is resolving inflammation or restoring normal tissue function. This mechanism is more generic and would account for the shutdown of auto-inflammatory responses as well as selecting the correct Th response for the clearance of pathogens [121, 122]. The major open question in mechanistic models for phenotype development based on success-driven feedback is that the feedback has to differentiate between the phenotypically different responses involved in the immune reaction. If antigen is cleared by one this website appropriate type of response, calling for a positive feedback for that phenotype, the other ongoing unsuccessful immune responses should still receive a negative feedback to let the memory phase be dominated by Th memory cells having a correct phenotype [99]. It remains unclear how a global signal such as ‘antigen clearance’ would feed back differentially into such local environments, and mechanistically, this seems

possible only if responses take place in different microenvironments. Following activation by APCs in draining lymph nodes, Th cells migrate to tissues after a few days selleck kinase inhibitor of activation and expansion in the lymphoid tissue. Because success can only be determined during the effector phase, success-driven feedback should be operating in the peripheral tissues rather than within secondary lymphoid organs. Evidence is accumulating that Th-cell phenotypes can be adjusted in peripheral tissues [125] and that T cells interact with APC in

nonlymphoid tissues [126-129]. Regardless of the precise cellular or Glutamate dehydrogenase molecular underpinnings, the effects of shutdown need to take place very locally. By assessing some measure of success in their immediate surroundings only, specific subsets of Th cells could be shut down, without affecting the responses in more successful microenvironments (Figure 4). For instance, Th-cell efficacy against cancer can be enhanced by depleting Treg cells from the tumour [130], illustrating that altering the Th-cell balance in tissues can have clinical effect. Compartmentalization would allow for synergy to occur between two Th-cell phenotypes, where their combined effects create the best response. Additionally, spatial segregation of different independent responses would allow for simultaneously generating responses to multiple pathogens that require different effector mechanisms at the same time. Memory formation would then preserve the outcome of successful decisions [99], rather than the outcome of previous instructive programmes.

The mice received a four-collagen–antibodies cocktail intravenously (i.v.) 10 days later (20 days after surgery, day 0). One week later, they received an intraperitoneal (i.p.) injection of LPS to enhance arthritis incidence and severity, and the experiment was terminated on day 14. Control

mice were injected with phosphate-buffered saline (PBS) i.v. and LPS i.p. Male transgenic ERE-luciferase mice were castrated and 11 days later immunized with chicken CII and adjuvant. After 9 days they received one subcutaneous injection of raloxifene, oestradiol or vehicle, and were then terminated 10 h later (day 10 after immunization). Mice were given subcutaneous injections 5 days per week of the raloxifene analogue LY117018 (generous gift from Eli Lilly, Indianapolis, selleck chemicals IN, USA) (60 µg/mouse/day) or 17β-oestradiol-3-benzoate (E2) (Sigma, St Louis, MO, USA) (1·0 µg/mouse/day)

dissolved in Miglyol812 (OmyaPeralta GmbH, Hamburg, Germany). Control mice received Miglyol812 (100 µl/mouse/day). The dosages of Ral and E2 have been shown previously to prevent osteoporosis equally well in mice [19–21]. LY117018 differs from raloxifene at only one site on the molecule, with a pyrrolidine ring on the basic side chain instead of a piperidine ring. This small difference does not affect its biological properties. Thus, selleck products Ral and LY117018 can be regarded as replaceable with respect to their biological properties. Experiment 1.  Two weeks after ovariectomy DBA/1 mice were immunized with 100 µg of chicken CII (Sigma, St Louis, MO, USA) dissolved in 0·1 m acetic acid and emulsified with an equal volume of incomplete Freund’s adjuvant (Sigma) supplemented with 0·5 mg/ml Mycobacterium tuberculosis (Sigma). A total volume of 100 µl was injected intradermally at the base of the tail. After 21 days, mice received Acesulfame Potassium a booster injection with CII emulsified in incomplete Freund’s adjuvant. Arthritis developed shortly thereafter, and was evaluated continuously for frequency and

severity. Experiment 2.  Twenty days after OVX or sham-operation, DBA/1 mice received an intravenous shot of a four-antibody cocktail [monoclonal immunoglobulin (Ig)G antibodies specific for the C1, J1, D3 and U1 epitopes on the collagen type II molecule], according to the protocol of Nandakumar and Holmdahl [10]. Non-arthritic controls received equal volumes of PBS. One week later, all mice received an intraperitoneal injection of 25 µg LPS (Escherichia coli 055 : B5; Difco Laboratories, Detroit, MI, USA). Experiment 3.  ERE-luciferase mice were immunized with 100 µg of chicken CII (Sigma) dissolved in 0·1 m acetic acid and emulsified with an equal volume of incomplete Freund’s adjuvant (Sigma) supplemented with 0·5 mg/ml M. tuberculosis (Sigma). A total volume of 100 µl was injected intradermally at the base of the tail.

[2] Macrophages

originate from circulating peripheral-blood monocytes that differentiate from common myeloid progenitors (CMP) in the bone marrow, which are also the common precursor for neutrophils, eosinophils, basophils, macrophages, DCs and mast cells. The haematopoietic growth factor colony-stimulating factor (CSF)-1 primarily controls the differentiation, maturation and survival of monocytes and macrophages. X-396 In response to CSF-1, monocytes differentiate from CMPs via the granulocyte/macrophage progenitor and macrophage/DC progenitor (MDP). Subsequently, these progenitors give rise to monoblasts, pro-monocytes and ultimately monocytes that are released into the circulation before entering tissues INCB024360 supplier to become resident tissue macrophages. Most

tissues and organs harbour a resident macrophage population that plays an important role in tissue homeostasis from their functional role in phagocytosis and matrix remodelling. However, there is growing evidence that monocytes can also differentiate into DCs depending upon the surrounding tissue microenvironment. This is particularly evident in non-lymphoid organs such as the kidney, where there is considerable phenotypic and functional overlap between macrophage and DC populations. Monocytes represent a heterogeneous population of cells and constitute approximately 10% and 4% of leukocytes in humans and mice, respectively.[3] Monocyte heterogeneity was initially discovered in humans over 20 years ago based on the differential expression of the antigenic markers CD14 and CD16.[4] This enabled the categorization of

human monocytes into three major subsets: CD14hiCD16−, CD14+CD16+ and CD14dimCD16+ cells (Table 1).[4, 5] CD14hiCD16− monocytes PJ34 HCl are referred to as ‘classical’ because their phenotype resembles the original description of monocytes, representing approximately 90% of total peripheral blood monocytes in a healthy person.[4, 6] In contrast, CD14+CD16+ monocytes, termed ‘non-classical’, constitute less than 10% of the total monocyte population and are phenotypically smaller and less dense. In patients with acute inflammation[7] and infectious diseases,[8, 9] monocyte numbers are significantly increased. Consequently, Grage-Griebenow et al.[5] identified an additional CD16+ monocyte population with reduced CD14 expression termed CD14dimCD16+ ‘intermediate’ monocytes. These monocytes represent approximately 5% of total blood monocytes and are functionally distinct from the CD14+CD16+ subset, with low phagocytic activity and high pro-inflammatory cytokine production, particularly tumour necrosis factor-α (TNF-α) and interleukin (IL)-1.

Additional work showed that the Mtb DosR-regulon-encoded antigen Rv2628 was strongly recognized by individuals with remote Mtb infection 13, 14. Thus far, the precise mechanisms and T-cell subsets responsible for the responses against Mtb DosR-regulon-encoded antigens have not been studied in detail; and virtually all studies have relied on measuring IFN-γ production by polyclonal

cells. Here, we report peptide reactivity and memory phenotypes of Mtb selleck compound DosR-regulon-encoded antigen-specific T cells in long-term LTBI, and moreover, document a large series of specific peptide epitopes recognized by specific CD4+ and CD8+ T cells. Three Mtb DosR antigens, Rv1733c, Rv2029c and Rv2031c (HspX, α-crystallin) were tested in this study. Strong Mtb DosR antigen-specific CD4+ and CD8+ polyfunctional T-cell responses were detected Rapamycin nmr in ltLTBIs. The highest responses were observed among single cytokine-producing CD4+ and CD8+ T-cell subsets (either TNF-α+, IL-2+ or IFN-γ+, depending on the stimulus) followed by double producing CD4+ and particularly CD8+ T cells. Of interest, the most frequent

multiple cytokine-producing T cells were IFN-γ+TNF-α+ CD8+ T cells. These cells were further characterized as effector memory (CCR7− and CD45RA−) or effector (CCR7− and CD45RA+) T cells, which have the ability to perform immediate effector functions. This is compatible with an important role for CD8+ T cells in Mtb infection 37, 38. Mtb antigen-specific polyfunctional T cells have been studied intensely the last few years, both in vaccination and in observational studies in Mtb-infected individuals 18–29, 39. There is currently

no consensus whether polyfunctional T cells represent a marker of protective immunity or of disease activity. The vaccine MVA85A (recombinant replication-deficient cAMP vaccinia Ankara, expressing Ag85A) induced polyfunctional CD4+ and CD8+ T cells producing IFN-γ, TNF-α and IL-2 as well as IFN-γ and TNF-α in mice, which correlated with TB protection 19. This vaccine also induced increased CD4+ T cells expressing IFN-γ, TNF-α and IL-2 in humans when given as a booster to previous BCG vaccination 20, 21. Similar results were reported following human vaccination with the BCG booster AERAS-402 (recombinant replication-deficient Adenovirus (Ad35) virus, expressing a polyprotein of Ag85A, Ag85B and TB10.4) 22. Finally, mice vaccinated with hybrid subunit vaccines H1 (Ag85-ESAT6) and H56 (H1+Rv2660) also had high numbers of triple cytokine-producing CD4+ T cells 23, 24. However, observational studies in humans have associated polyfunctional CD4+ T cells with TB disease 25, 26.

This is important as the concentration of complement proteins in serum is very high. Therefore, to inhibit complement activity in totality, either a set of inhibitory proteins or a multicomplement-binding protein could fulfil such a requirement. The complement proteins usually act on the surface of target pathogens. However, blocking of complement activation in blood-sucking H. contortus is all the more important as antibodies formed against the internal proteins of the parasite during infection

[42] in combination with complement proteins (acquired during blood meal) would damage the internal tissues with serious consequences for the parasite. Identification of H.c-C3BP should facilitate development of new therapeutics considering a key role of this protein in immune modulation. We thank Director, IVRI, Vincristine nmr for providing the necessary facilities, Prof. Anil K Jaiswal, University of Maryland, USA, for mass spectrometry. This work was supported by a grant from the Department of Biotechnology, Government of India, to PJ. “
“Plasmacytoid dendritic cells (PDC) are involved in innate immunity by interferon (IFN)-α production,

and in adaptive immunity by stimulating T cells and inducing generation of regulatory T cells (Treg). In this study we studied the effects of mammalian target of rapamycin (mTOR) inhibition by rapamycin, a commonly used immunosuppressive and anti-cancer drug, on innate and adaptive immune functions of human PDC. A clinically relevant concentration Saracatinib order of rapamycin inhibited Toll-like receptor (TLR)-7-induced IFN-α secretion potently (−64%) but TLR-9-induced IFN-α secretion only slightly (−20%), while the same concentration suppressed proinflammatory cytokine production by TLR-7-activated and TLR-9-activated PDC with similar

efficacy. Rapamycin inhibited the ability of both TLR-7-activated and TLR-9-activated PDC to stimulate production of IFN-γ and interleukin (IL)-10 by allogeneic T cells. Surprisingly, mTOR-inhibition enhanced the capacity of TLR-7-activated PDC to stimulate naive and memory T helper cell proliferation, which was caused by rapamycin-induced Chloroambucil up-regulation of CD80 expression on PDC. Finally, rapamycin treatment of TLR-7-activated PDC enhanced their capacity to induce CD4+forkhead box protein 3 (FoxP3)+ regulatory T cells, but did not affect the generation of suppressive CD8+CD38+lymphocyte activation gene (LAG)-3+ Treg. In general, rapamycin inhibits innate and adaptive immune functions of TLR-stimulated human PDC, but enhances the ability of TLR-7-stimulated PDC to stimulate CD4+ T cell proliferation and induce CD4+FoxP3+ regulatory T cell generation. Plasmacytoid dendritic cells (PDC) have important functions in innate and adaptive immunity. They are unique in rapidly producing massive amounts of type I interferon upon recognition of viral nucleotides or self-DNA-protein complexes by their Toll-like receptors (TLR).

An alternative approach is to preclude IFN production by disarming or degrading the transcription factors involved in the expression of IFN, such as interferon regulatory factor 3 (IRF3)/IRF7, nuclear factor-κB (NF-κB), or ATF-2/c-jun, or by inducing a general block on host cell transcription. Viruses also oppose IFN signalling, both by disturbing the type I IFN receptor and by impeding JAK/STAT signal transduction upon IFN receptor engagement.

In addition, the global expression of IFN-stimulated genes (ISGs) can be obstructed via interference with epigenetic signalling, and specific ISGs can also be selectively targeted for inhibition. Finally, some viruses disrupt IFN responses by co-opting negative regulatory systems, whereas others use antiviral mechanisms drug discovery to their own advantage. Here, we review recent developments in this field. Despite almost constant exposure to pathogens, mammals are only rarely infected to the point where disease Trichostatin A purchase becomes evident. The first line of defence consists of the interferon (IFN) family of soluble cytokines. The IFNs have anti-cancer, anti-proliferative, anti-viral and immunomodulatory functions[1] through the expression of more than 300 IFN-stimulated genes (ISGs).[2] There are three classes of IFNs which are produced by different cell types, bind unique receptors and have distinctive biological actions.[3] Here,

we focus on the type I IFNs, which are produced 4��8C by most cell types and have potent, inherent antiviral activity.[4] The type I IFN response is bimodal: first, detection of an invading virus leads to IFN production and secretion and second, IFN acts in an autocrine and paracrine manner to induce ISGs, the products of which work collectively to disrupt viral replication and

spread. To generate a productive infection, viruses must overcome antiviral responses, and accordingly, every aspect of these defences is targeted for inhibition. Here, we describe the IFN response and viral immune evasion strategies. As this topic has been extensively reviewed previously, we will focus on the most recent advances. In the first step of the biphasic type I IFN response, virus is detected through the recognition of pathogen-associated molecular patterns (PAMPs), highly conserved structural features found in broad classes of pathogens. PAMPs are sensed by pattern recognition receptors (PRRs), including the toll-like receptors (TLRs).[5] The TLRs recognize viral components including glycoproteins and nucleic acids such as dsRNA or CpG DNA. Via their cytoplasmic Toll/interleukin-1 receptor (TIR) domains, TLRs recruit TIR-containing adaptors such as MyD88, TIR-domain-containing adapter-inducing IFN-β (TRIF), Mal and TRIF-related adaptor molecule (TRAM), leading to the activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) (Fig. 1). Recently, several viruses have been found to disrupt TLR signalling by interfering with the adaptor molecule TRIF.