Four images of different

sectors of the section selected at random while out of focus were then focused, captured and analysed from each sample. From each image, 10 different regions were randomly selected. However, if the region was in the centre of the fibre, on an area of fibrosis, on a neuromuscular junction or if more than one measurement per fibre was selected, the region was moved slightly to the nearest fibre membrane. The measured regions included both a portion of the cytoplasm and the sarcolemma (Figure 1A). The principles of this technique are the following: when excited, fluorescent labelled antibodies bound to the proteins release photons Tanespimycin ic50 that are captured by the charge-coupled device, and converted into electrons. The number of electrons, which is directly proportional to the intensity of the fluorescence, is then mapped on to an image in MetaMorph and presented as an intensity value (Figure 1B,C). The dynamic range of the camera a 12-bit Photometrics CoolSnapHQ2 [Leica Microsystems (UK) Ltd, Milton Keynes, UK] was 0–4095 intensity units and our measurements were taken so that pixel saturation was avoided (all our intensity measurements were well

below the saturation limit). Intensity measurements of these regions were logged into a spreadsheet Dorsomorphin for data analysis. For each antibody used, 40 different measurements from each sample were taken. Each region where intensity values were measured contained a portion of the cytoplasm and of the sarcolemma, reflecting the location of the proteins of interest. For each region, the minimum intensity value recorded (representative of the cytoplasm or background intensity) was subtracted from the maximum intensity value (which corresponded to the sarcolemma) to correct each measurement for Resveratrol background intensity. To correct for variation of sarcolemmal integrity between samples,

we performed the same measurements on serial sections stained with a β-spectrin antibody. The spectrin intensity values obtained for the control samples were set as the standard to calculate normalization factors. For each of the antibodies, the minimum intensity value was subtracted from the maximum, then these values (one per each of the 40 fibres analysed) were normalized with the β-spectrin measurements and plotted on a graph. Data are presented in scatter plots and summarized as a ratio of the control. Statistical analysis of the data was performed using one-way analysis of the variance. We compared muscle sections taken from a normal control, a DMD patient, a BMD patient and a manifesting carrier, using two dystrophin antibodies (Dys2 and P7). We also studied in parallel the intensity of dystrophin-associated complex proteins (ASG, BDG) and UTR (Figure 2A).

Increasing numbers of APC were co-cultured in round-bottom 96-well plates and in complete medium with 105 CFSE-labeled OT-II cells previously enriched by negative selection using a cocktail of PE-labeled mAb, anti-PE microbeads (Miltenyi) and LD columns (Miltenyi). At day 5, CFSE dilution was determined by flow cytometry. A fixed number of Calibrite™ beads (BD) were added

to each sample to quantify the absolute number of OT-II cells per well. Naïve CD4+ T cells, defined as CD25−FR4−CD62LbrightCD44lowCD4+, were purified from CD4-enriched (Dynal® Mouse CD4 PLX3397 chemical structure negative isolation kit, Invitrogen) spleen and total lymph node cells on a MoFlo™ or FACSAria™ (BD) cell sorter. The population was routinely more than 98% pure and free of Foxp3+

cells (not shown). Before transfer, T cells were labeled with 2 μM of CFSE, washed and resuspended in PBS. An amount of 1–2×106 cells were adoptively transferred into CD45.1+ or CD45.2+ congenic B6 mice. One day later, mice were injected i.v. or in the footpad with indicated amount of OVA323–339-coupled mAb alone or in combination with 40 μg this website poly I:C or 100 μg curdlan. CD4+ T-cell responses were assessed 4–6 days after immunization or at the indicated time points. Red-blood-cell-depleted splenocytes were restimulated in complete medium with either 10 μg/mL of OVA323–339 peptide or 10 ng/mL of PMA (Sigma) and 1 μg/mL of ionomycin (Calbiochem). After 30 min, Brefeldin A (Sigma) was added to the culture at a final concentration of 10 μg/mL, and the cells were incubated for three more hours. Alternatively, in some experiments, splenocytes were restimulated for 3 days in complete medium with or without 10 μg/mL of OVA323–339 peptide. Cytokine accumulation in the supernatant was then monitored by ELISA. Flat-bottom 96-wells plates (MaxiSorp™ Nunc-immunoplates) were coated with 2 μg/mL of 7H11 mAb. After overnight CYTH4 incubation, unbound mAb was washed away (PBS, 0.05% Tween 20) and non-specific binding sites were blocked with PBS supplemented with 2.5% FBS and 0.2% NaN3. Serially diluted sera were then plated and incubated for 6 h

at room temperature. After six washes, bound Ab were detected with biotinylated anti-mouse IgG1 (B68-2, BD) or anti-mouse (5.7, BD) mAb or with biotin-SP-conjugated anti-mouse IgG F(ab′)2 (Jackson Immunoresearch). Plates were then washed extensively and incubated with extravidin®-conjugated alkaline phosphatase (Sigma). After six washes, the presence of bound Ab was revealed using p-Nitrophenyl phosphate (Sigma). Wells were considered as positive when the value of the absorbance measured at 405 nm was superior to the one obtained with the serum from a PBS-injected mouse+3x SEM. The Ab titer corresponds to the last dilution scoring positive. This study was funded by Cancer Research UK. C. R. S. acknowledges the support of the Fondation Bettencourt-Schueller.

Donor proteinuria in the absence of other significant factors influencing organ acceptance, appears to be of little importance in influencing graft outcome. Larger studies are required to further examine this. 254 AMBULATORY VS OFFICE BLOOD PRESSURE MONITORING IN RENAL TRANSPLANT RECIPIENTS J AHMED, V OZORIO, M FARRANT, W VAN DER MERWE North Shore hospital, BGJ398 purchase Auckland,

New Zealand Aim: To investigate correlation between office (OBPM) and ambulatory (ABPM) blood pressure monitoring in renal transplant recipients (RTR). Background: Hypertension is common post renal transplant and has adverse effects on cardiovascular and graft health. Nocturnal hypertension, which is also implicated in poor outcomes, can only be diagnosed via ABPM. ABPM is increasingly being recognized as a better method of measuring BP with discrepancies between office (oBP) and ambulatory BPs (aBP) being noted in RTR. Methods: We undertook a retrospective analysis of 98 renal transplant recipients (RTR) (40% female, average age 55) in our unit and compared oBP and aBP recordings. Baseline demographic data was recorded along with Small molecule library eGFR, proteinuria, medications and co-morbidities. Results: ABPM revealed 28.5% and 13.2% had concordant normotension and hypertension

respectively. There was a discordance between OBPM and ABPM in 58% of patients with 53% due to masked hypertension (of which 34% were due to isolated nocturnal hypertension) and 5% had white coat hypertension. Overall mean systolic BP was 3.6 mmHg (0.5–6.5) and diastolic BP 7.5 mmHg (5.7–9.3) higher via ABPM than

OBPM (95% confidence). This was independent of eGFR, proteinuria, transplant time/type and comorbidities. 41% of patients had their management changed after results from ABPM. Conclusions: There is a significant discordance between OBPM and ABPM with a predominance of masked hypertension. The results of ABPM changed management Methocarbamol in a significant proportion of patients. ABPM is the only means to diagnose nocturnal hypertension and should be routinely offered as part of hypertension management of RTR. 255 ANNUAL SKIN CANCER INCIDENCE IN RENAL TRANSPLANT RECIPIENTS 1997–2013: A SINGLE CENTRE EXPERIENCE G DAS1, B TAN1,2, K NICHOLLS1,3 Departments of 1Nephrology and 2Dermatology, The Royal Melbourne Hospital, Melbourne; 3Department of Medicine, The University of Melbourne, Melbourne, Australia Aim: To evaluate annual incidence of skin cancers (SC) in renal transplant recipients (RTR) in our hospital (RMH) from 1997 to 2013. Background: ANZDATA data indicates that RTR have a 100 fold increased risk of developing SCC. There is no clear evidence that SC incidence has fallen over time, or with different immunosuppressive regimens. Methods: We retrospectively studied RMH patients transplanted between January 1997 and December 2013, extracting data from medical records, our departmental database, and pathology reports.

The data confirm previously published studies at other centers. “
“The activation of TLRs expressed by macrophages or DCs, in the long run, leads to persistently impaired functionality. TLR signals activate a wide range of negative feedback mechanisms; it is not known, however, which of these can lead to long-lasting tolerance for further stimulatory signals. In addition, it is not yet understood how the functionality of monocyte-derived DCs (MoDCs) is influenced in inflamed tissues by the continuous RAD001 solubility dmso presence of stimulatory

signals during their differentiation. Here we studied the role of a wide range of DC-inhibitory mechanisms in a simple and robust model of MoDC inactivation induced by early TLR signals during differentiation. We show that the activation-induced suppressor of cytokine signaling 1 (SOCS1), IL-10, STAT3, miR146a and CD150 (SLAM) molecules possessed short-term inhibitory effects on cytokine production but did not induce persistent DC inactivation. On the contrary, the LPS-induced IRAK-1 downregulation could alone lead to persistent MoDC inactivation. Studying cellular functions in line with the activation-induced

negative feedback mechanisms, we show that early activation of developing MoDCs allowed only a transient cytokine production that was followed by the downregulation of effector functions and the preservation of a tissue-resident non-migratory phenotype. In response to pathogen recognition or inflammatory Pifithrin-�� nmr mediators, steady-state tissue-resident DCs exit the inflamed tissues and transport peripheral antigens to secondary lymphoid organs, where DCs can initiate the adaptive immune response by triggering naïve T-cell activation. At the same

time, monocytes enter the inflamed tissues and give rise to phagocytic cells and APCs, including DCs, thereby compensating the rapid egress of the steady-state DC network 1–3. The newly differentiated monocyte-derived DCs (MoDCs) may act as local tissue resident APCs or as sources of inflammatory cytokines 4, 5. In addition, these cells might obtain the ability to migrate to peripheral lymphoid organs maintaining the activation of naïve T lymphocytes 2, 6. Human monocytes obtain DC-like features when maintained 2-hydroxyphytanoyl-CoA lyase in culture for 5–8 days in the presence of GM-CSF combined with IL-4 or other cytokines 7, 8. During their differentiation MoDCs downregulate CD14, upregulate CD1a and DC-SIGN and obtain the ability to express CCR7 upon activation that is required for migration towards lymphoid tissues. However, such differentiation of immature MoDCs is highly unlikely to occur in inflamed tissues where the developing cells constantly receive stimulatory signals due to the presence of microbial compounds, inflammatory mediators and tissue damage. It has been extensively documented that long-term activation leads to functional exhaustion of macrophages and DCs 9.

Instead, immune responses contribute to the tissue damage.

However, this may depend on localization of infection in the upper conductive or in the peripheral respiratory zone. To study this we produced two distinct sizes of small alginate beads (SB) and large beads (LB) containing P. aeruginosa. In total, 175 BALB/c mice were infected with either SB or LB. At day 1 the quantitative bacteriology was higher in the SB group compared to the LB group (P < 0·003). For all time-points smaller biofilms were identified by Alcian blue staining in the SB group (P < 0·003). Similarly, the area of the airways in which biofilms were identified were smaller (P < 0·0001). A shift from exclusively endobronchial to both parenchymal PS-341 ic50 and endobronchial localization of inflammation from day 1 to days 2/3 (P < 0·05), as well as a faster resolution of inflammation at days 5/6, was observed in the SB group (P < 0·03). Finally, both the polymorphonuclear neutrophil leucocyte (PMN) mobilizer granulocyte colony-stimulating factor (G-CSF)

and chemoattractant macrophage inflammatory protein-2 (MIP-2) were increased at day 1 in the SB group (P < 0·0001). In conclusion, we have established a model enabling studies of host responses in different pulmonary zones. An effective recognition of and a more pronounced host response to infection in the peripheral zones, indicating that increased lung damage was demonstrated. Selleck Crizotinib Therefore, treatment of the chronic P. aeruginosa lung infection should be directed primarily at the peripheral lung zone by combined intravenous and inhalation antibiotic treatment. Most patients

with the inherited disease cystic fibrosis (CF) acquire a chronic lung infection with Pseudomonas aeruginosa. Once chronic P. aeruginosa lung infection is established it is almost impossible to eradicate, despite relevant antibiotic treatment and substantial innate and adaptive host responses. The background for the tolerance of the chronic P. aeruginosa Adenosine triphosphate lung infection to antibiotics and host responses is the formation of biofilms, where the bacteria are organized in micro colonies surrounded by an extracellular matrix. Because the infection remains in the lungs, continuous induction of pulmonary inflammation and stimulation of the adaptive immune response is the result. In fact, both parts of the host immune response contribute to the lung pathophysiology. The constantly recruited polymorphonuclear neutrophil leucocytes (PMNs) contribute by release of exoproteases, reactive oxygen and nitrogen species, and the induced T helper type 2 (Th2)-dominated response contributes by induction of a pronounced antibody response resulting in immune complex disease [1]. The activation and recruitment of the host response is, however, not uniform throughout the lung.

From this paper, we extracted an affinity-balanced

set of 12 peptide pairs of immunogenic and nonimmunogenic binders, and tested both affinity and stability of their interaction with HLA-A*02:01. By and large, we confirmed the reported affinity data. Importantly, we found a highly significant correlation between high stability and immunogenicity (a half-life of 14 h for the immunogenic binders versus 3 h for the nonimmunogenic binders, p = 0.0007). Thus, this affinity-balanced reanalysis of the unbiased data reported by Sette and colleagues confirms that the stability of pMHC-I complexes contributes to the definition of immunogenicity, and that stability is a better indicator of immunogenicity than affinity is. This experimental analysis was subsequently corroborated by a bioinformatics-driven analysis. Our data suggest that the description and relative contribution of antigen Everolimus molecular weight processing and presentation events needs to be redefined. Nonimmunogenic binders are usually considered to be the result of “holes in the T-cell repertoire.” However, a failure to achieve stable interaction with MHC may be considered an alternative mechanism of lacking immunogenicity, as a “hole in the stably bound MHC repertoire”

mechanism, which would go unnoticed when solely addressing the affinity of peptide-MHC-I interactions. This may account for as much as 30% of these instances of lacking immunogenicity and it follows that a method

to predict the stability of pMHC-I complexes might support computational CTL epitope discovery. ROS1 Finally, both our experimental and bioinformatics-driven this website analysis suggested that the lack of stability of HLA-A*02:01 binding occurred when the P2 anchor residue was not optimal. Although both threonine and glutamine can be found in P2 of high-affinity binding peptides, they lead to a seven to tenfold reduction in stability compared to the optimal leucine. Thus, it would appear that one anchor might be sufficient for binding, whereas two anchors might be needed to obtain stable MHC-I interaction. This is reminiscent of a previous suggestion that the different pockets of the MHC-II can be seen as interacting with peptide independently, and that destabilizing any of the pockets individually may lead to peptide dissociation [[39]]. Thus, pMHC-I stability studies should help elucidating how peptide bind and remain bound to MHC-I, and how MHC-I matures and eventually becomes a bona fide CTL target. Peptides were synthesized by Schafer-N (Copenhagen, Denmark) by Fmoc chemistry and HPLC purified to at least more than 80% (usually >95%), analyzed by HPLC and MS, and quantitated by weight. Synthetic genes encoding MHC-I heavy chains were generated as previously described [[40, 41]]. Briefly, genes encoding MHC-I heavy chains truncated at position 275 (i.e.

“
“Regulatory T (Treg) cells represent one of the main mechanisms of regulating self-reactive immune cells. Treg cells are thought to play a role in down-regulating immune responses to self or allogeneic antigens in the periphery. Although the function of Treg cells has been demonstrated in many experimental settings, the precise mechanisms and antigen specificity often remain unclear. In a hepatitis B e antigen–T-cell receptor (HBeAg-TCR)

double transgenic mouse model, we observed a phenotypically unique (TCR+ CD4−/CD8− CD25+/− GITRhigh PD-1high FoxP3−) HBeAg-specific population that demonstrates immune regulatory function. This HBeAg-specific double-negative regulatory cell population proliferates vigorously in vitro, in contrast to any other known regulatory population, selleck products in an interleukin-2-independent manner. The primary function of the immune system

is to protect the self from pathogens. A highly effective and dynamic cellular network has evolved to signal the presence of pathogens and initiate a response that is specific for the invading pathogen while maintaining tolerance to self. Distinguishing between self and non-self is a fundamental property of the immune system and is accomplished by a variety of mechanisms. A function of regulatory T (Treg) cells INK 128 mouse is to prevent self-reactive immune cells from damaging self. The Treg cells, particularly CD4+ CD25+ conventional Treg (cTreg) cells, are thought to play a role in down-regulating immune responses to self or allogeneic antigens in the periphery.1–4 Although the function of Treg cells has been shown in a number of in vivo models of autoimmunity and transplantation, the precise mechanism and antigen specificity often remains unclear.5 In 1971 it was first suggested that Treg cells had the ability to transfer antigen-specific tolerance to naive animals.6 Even though a role for regulatory cells during an immune response was widely accepted, the existence of Treg cells was controversial until a specific however surface marker was described by Sakaguchi et al.7 Conventional Treg cells constitutively express a variety of cell

markers, such as CD4, CD25, CD45RBlow, CD62 ligand (CD62L), CD103, as well as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR).7–14 Although cTreg cells express CD4+ CD25+, CD25 is not a specific marker for cTreg cells. Other cell markers (i.e. CTLA-4, GITR and CD103) are also not exclusive markers for Treg cells, because in most cases they are up-regulated on effector T cells upon activation. The transcription factor Forkhead box P3 (FoxP3) is predominantly expressed on Treg cells and appears to be expressed at the thymic CD4+/CD8+ stage.15–18 In contrast to the cell surface markers mentioned above, FoxP3 is not observed in non-Treg cells upon activation or differentiation into T helper type 1/ type 2 cells, nor in natural killer T cells.

01). To further validate the in vivo findings in our aGvHD model, we also tested the functional capacity of our aTreg cells to prolong allogeneic skin graft survival. As depicted in Figure 5, 1 day prior to transplantation,

C57BL/6Rag–/– mice were reconstituted with 2 × 105 CD4+CD25+ aTreg cells isolated from primary cultures together with 1 × 105 CD8+ and 1 × 105 CD4+CD45RBhigh T cells. As a control, we included a group receiving Teff cells only. aCD4+TGF-β+RA aTreg cells prolonged graft survival compared to mice reconstituted with aTreg cells from untreated or aCD4-only treated cultures (*p ≤ 0.5) (Fig. 5B). In contrast, Fulvestrant cell line aCD4+Rapa aTreg cells did not perform better than aTreg cells obtained from aCD4-only treated cultures. Interestingly, animals receiving aCD4+TGF-β+RA aTreg cells showed also an improved recovery and weight gain after transplantation compared with mice receiving aTreg cells from all other groups (Fig. 5C). Here, we present an optimised protocol for in vitro generation of murine aTreg cells with improved in vivo function in two independent models of transplantation tolerance. This could be accomplished by addition of TGF-β+RA or Rapa PI3K inhibitor to our previously described aCD4-mAb Treg-cell expansion protocol [16]. Notably, the optimised aTreg-cell expansion

protocol increased aTreg-cell frequencies and absolute aTreg-cell counts while reducing the number of undesired Teff cells. The aTreg cells were predominantly generated by an expansion of nTreg cells. Helios and Neuropilin-1 expression levels,

stability of the aTreg phenotype, and the suppressive in vitro and in vivo function exceeded in our novel aCD4+TGF-β+RA Treg protocol over all other protocols including addition of Rapa. Several protocols for the generation alloreactive T cells with regulatory function, shown to suppress anti-donor immune responses, have been described in addition to our anti-CD4mAb-based Methamphetamine protocol. These include IL-10-mediated induction of Tr1 cells [28, 29], stimulation with allogeneic APCs or peptide-pulsed APCs in the presence of TGF-β [30-32], ex vivo costimulatory blockade [33] or IFN-γ-conditioned stimulation with alloantigen [34, 35]. In addition, vitamin D or Rapa-conditioned tolerogenic DCs have been used to generate T cells with alloreactive regulatory functions [36-38]. It will be of importance in future investigations which of these strategies is the most superior one. It was also shown that Rapa induces human Treg cells from conventional CD4+ T cells in vitro [39] as well as in vivo [40, 41]. In our experiment, Rapa increased the generation of murine aTreg cells only in combination with aCD4. The ability of TGF-β to induce Treg cells has been known for a long time [42]. Wan and Flavell showed that TGF-β is essential to keep the functionality of CD4+CD25+Foxp3+ in the periphery and that TGF-β has the potential to induce Foxp3 in naïve cells [43].

One important facet is the circulatory system dysfunction, which includes capillary bed plugging. This review addresses the mechanisms of capillary plugging and highlights our recent discoveries on the roles of NO, ROS, and activated coagulation in platelet adhesion

and blood flow stoppage in septic mouse capillaries. We show that sepsis increases platelet adhesion, fibrin deposition and flow stoppage in capillaries, Selleckchem Liproxstatin 1 and that NADPH oxidase-derived ROS, rather than NO, play a detrimental role in this adhesion/stoppage. P-selectin and activated coagulation are required for adhesion/stoppage. Further, platelet adhesion in capillaries (i) strongly predicts capillary flow stoppage, and (ii) may explain why severe sepsis is associated with a drop in platelet count in systemic blood. Significantly, we also show that a single bolus of the antioxidant ascorbate (injected intravenously at clinically relevant dose of 10 mg/kg) inhibits adhesion/stoppage. Our data suggest that eNOS-derived NO at the platelet-endothelial interface is anti-adhesive and required Selleckchem PLX 4720 for the inhibitory

effect of ascorbate. Because of the critical role of ROS in capillary plugging, ascorbate bolus administration may be beneficial to septic patients whose survival depends on restoring microvascular perfusion. “
“Please cite this paper as: Wijnstok N, Hoekstra T, Eringa E, Smulders Y, Twisk J, Serne E. The relationship of body fatness and body fat distribution with microvascular recruitment: The Amsterdam Growth and Health Longitudinal Study. Microcirculation 19: 273–279, 2012. Introduction:  Microvascular function has been proposed to link body fatness to CVD and DM2. Current knowledge of these relationships is mainly based on studies in selected populations of extreme phenotypes. Whether these findings can be translated to the general population remains to be investigated. Aim:  To assess the relationship of body fatness and body fat distribution with microvascular function in a healthy population-based cohort. Methods:  Body fatness parameters were obtained by anthropometry and whole-body dual-X-ray absorptiometry (DEXA) in 2000 and 2006. Microvascular

recruitment (i.e., absolute increase in perfused capillaries after arterial occlusion, using nailfold capillaroscopy) was measured in 2006. Linear regression analysis was used to examine the Oxaprozin relationship of (changes in) body fatness and body fat distribution with microvascular recruitment. Results:  Data were available for 259 participants (116 men). Capillary density was higher in women than in men (difference 7.3/ mm2; p < 0.05). In the total population, the relationship between total body fatness and microvascular recruitment was positive (β = 0.43; p = 0.002), whereas a central pattern of fat distribution (trunk-over-total fatness) showed a negative relationship (β = −26.2; p = 0.032) with microvascular recruitment. However, no association remained apparent after adjustment for gender.

In conclusion, we present novel data showing that extensive endoscopic image-guided sinus surgery followed by antibiotic irrigation without additional immunosuppressive treatment decreases IgA and IgG BPI-ANCA levels in patients with CF and also confirm the same effect following lung transplantation. We hypothesize that extensive surgery eradicating infectious foci and a reduction in mucosal inflammation can influence the pathogenic process of autoantibody production, for example BPI-ANCA. Our results are in favour of applying EIGSS in CF patients with intermittent or chronic sinus infections

and also indicate that measuring BPI-ANCA levels in individual patients may be used as a surrogate marker for guiding further therapeutic interventions. We would like to thank Lena Nørregaard, the laboratory Small molecule library technician at the Department of Clinical Microbiology, Rigshospitalet, the laboratory technicians Y-27632 in vitro at EuroDiagnostica AB and statistician Severin

Olesen Larsen, Statens Serum Institut, for their helpful assistance. The serum analyses performed by EuroDiagnostica AB were financed by Statens Serum Institut. This work was supported by the Candys Foundation, a non-profit organization. Jørgen Wieslander is employed at EuroDiagnostica AB. “
“With increasing interest in alternative options to interferon-alpha-based treatments, IFN-λ has shown therapeutic promise in a variety of diseases. Although

the antiviral activity oxyclozanide of IFN-λ has been extensively studied, there is limited knowledge regarding the immunological functions of IFN-λ and how these differ from those of other classes of IFNs. In this study, we investigated the effects of IFN-λ on primary human NK cells, both in a direct and indirect capacity. We demonstrate that in contrast to interferon-alpha, IFN-λ is unable to directly stimulate NK cells, due to the absence of IFN-λ receptor chain 1 (IFN-λR1) on NK cells. However, IFN-λ, in combination with TLR4 challenge, is able to induce the production of select members of the IL-12 family of cytokines in monocyte-derived macrophages. We further show that through macrophage-mediated IL-12 production, IFN-λ is able to indirectly affect NK cells and ultimately induce IFN-γ production. “
“Currently, little information is available regarding innate immunity to helminthic parasite infection. In this study, we isolated the excretory–secretory (ES) proteins from Anisakis simplex (sea mammal intestinal parasite) third stage larva. We determined that the levels of IL-17 in the lung and lung draining lymph node of mice were increased sixfold as a result of intranasal treatment with ES proteins.