On average, 25% of macrophage-associated conidia are phagocytosed after 1 h, 16% of these cell-associated conidia are killed after

4 h and conidial germination was inhibited in more than 95% of the conidia of A. fumigatus.[53] Comparable studies on zygomycetes would gain insights into the clearance of the fungal burden and forecast the potential of zygomycetes as causative agents of emerging fungal diseases. Moreover, transcriptomic analysis will help to understand the virulence and survival mechanism of the fungi when it confronts macrophages, e.g. the role of chromatin MI-503 remodelling as a central regulator of survival strategies which facilitates a reprogramming of cellular energy metabolism in macrophage-internalised fungal cells and provide protection against DNA damage as shown for Candida glabrata.[54] Many studies have established that virulence factors can be differentially expressed as a function of experimental conditions,

but clinical isolates of Cryptococcus neoformans behave differently under the same experimental conditions, a diversity that could participate in the variable outcome of infection in humans.[55] It has been hypothesised that the survival strategies for soil-borne, potentially human pathogenic fungi (e.g. C. neoformans) after ingestion by macrophages and amoebae were similar.[56] Consequently, check details it will be worthwhile to compare the mechanisms of phagocytosis with amoebae which served as interacting partners in the environment resulting in a training of the fungal pathogen to successfully cope with the amoeboid immune cells of the human immune system towards adaption to the human host during evolution. Just recently, the whole genome of Acanthamoeba castellanii (Ac) was determined, the first representative from a solitary free-living amoebozoan.[57] Ac utilises a diverse repertoire of predicted

pattern recognition receptors, many with predicted orthologous functions in the innate immune systems of higher organisms.[57] The exploration of the Tacrolimus (FK506) connection between both, receptors of amoebae and immune cells will shed light into the evolutionary origin of the interplay between fungal pathogen and innate immune cells. This work was financially supported by the Deutsche Forschungsgemeinschaft (DFG) Jena School for Microbial Communication (JMRC project #66) and within CRC/TR 124 FungiNet: project Z1 to KV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We express our gratitude to Paul M. Kirk (Royal Botanic Gardens Kew, UK) for providing the numbers of species for the subphyla and orders of the zygomycetes. The authors declare that no conflict of interest exists. “
“This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases (IFDs) in patients with haematological malignancies.

[107] Immunohistochemistry localized p65 to CEC nuclei in Pkd1−/− kidney explants.[107] Similarly, Park et al. identified an unspecified phosphorylated NF-κB protein in CEC nuclei and in tubules surrounding the cysts of PKD2 mice and human ADPKD kidneys.[20]

Increased levels of phosphorylated and unphosphorylated NF-κB protein, and phosphorylated-IKKα/β were observed in PKD2 mice compared with wild-type mice, as well as increased levels of RAGE (receptor of advanced glycation end product, which is associated with renal inflammatory cell migration)[108] and s100a8 and s100a9 (inflammation-associated calcium binding proteins).[20, 109] In PKD2 mice, RAGE was located in CEC, and s100a8/a9 in CEC and interstitial areas proximate to inflammatory cells.[20] These data suggest that NF-κB activation is upregulated in human and animal models of PKD, and may be associated with increased inflammatory PLX4032 price mediators. Moreover, Qin et al. demonstrated that NF-κB inhibition modulated cystic disease, resulting in a three-fold decrease in histological cyst area.[107] NF-κB inhibition diminished the mRNA expression of three upregulated genes in PKD2 kidney explants: Wnt7a and Wnt7b, which are believed to be involved in polar cell polarity,[110] and Pax2, which is involved in embryonic nephron development.[107, 111, 112] NF-κB thus provides a promising

target for therapy, though further studies are required to characterize the effects, if any, of NF-κB on inflammation in PKD. Inflammation in PKD may be Torin 1 caused by abnormal regulation of the JAK-STAT pathway. Receptor binding of cytokines (e.g. IL-6 and interferon-γ), activates JAK proteins, which in turn activate STAT (signal transducer and activator of transcription) proteins, leading to gene transcription.[113] In vitro studies have shown that PC1 and PC2 are required for JAK1 and JAK2 activation,[114] and that Pkd1 regulates STAT3.[114] Therefore, Pkd1/2 mutations may promote inflammation by interrupting the control of JAK-STAT signalling. Furthermore, the JAK-STAT pathway is regulated by the suppressors of cytokine signalling (SOCS),[115] such as SOCS-1, which limits

the inflammatory activity of cytokines and macrophages.[116] Reverse transcriptase SOCS-1 knockout has led to the development of polycystic kidneys in mice,[117] but it is unknown whether this effect was mediated by inflammation or other facets of JAK-STAT signalling. Interstitial inflammation appears to correlate with disease progression in PKD. For example, heterozygous Han:SPRD rats display increased inflammatory cells at late stages of disease when there is severe interstitial fibrosis, proteinuria and extensive cystic expansion.[34] Given this, is it possible that inflammation induces cystogenesis? In some interventional studies, the amelioration of interstitial inflammation is accompanied by reduced cyst growth,[118, 119] though this does not prove causality.

9×106 total cells/mouse; n = 9; and 54% B-1 cells). Thus, these data confirmed the presence of significant numbers of B-1 cells in the steady-state BM, where they are of a phenotype comparable with that of spleen but not PerC B-1 cells. To determine whether B-1 cells are the IgM-secreting cells in the BM we examined spontaneous IgM secretion in Ig-allotype-chimeric mice. Confirming our data from BALB/c mice (Fig. 1A), little spontaneous natural IgM secretion was detected by PerC B-1 cells (0.03 μg/mL from 2×105 total cells) in these animals (Fig. 4A). In contrast, higher concentrations of B-1 cell-derived IgM were found in cultures of spleen (0.72 μg/mL) and BM (0.73 μg/mL) (Fig.

4A). As BM cultures contained about 3-fold lower numbers learn more of IgM AFCs than spleen cultures (2.9±0.6×103 and 8.5±0.2×103 IgM AFCs per 106 cells respectively) antibody production per secreting cell was

highest in the BM. In the spleen, about 87% of natural IgM secreting cells were of B-1 (Igh-a) Alpelisib ic50 cell origin and in the BM that number was at least 95% (Fig. 4B). Given that 10–20% of host-derived Igh-b could be B-1 cells in the allotype-chimeras 26, we conclude that the IgM AFCs in spleen and BM are B-1 cells. In addition, comparing the frequencies of B-1 cells in spleen and BM and the number of AFCs, indicated that >80% of BM B-1 cells secreted IgM, whereas for spleen this number was closer to 40% (Fig. 4C). Consistent with results Fossariinae from BALB/c mice (Fig. 1E), a subset of spontaneous IgM-secreting B cells recognized influenza A/Mem/71, both in spleen and BM of Ig-allotype chimeras (Fig. 4D), further demonstrating that they are natural IgM-secreting

B-1 cells. To further demonstrate the role of BM B-1 cells in spontaneous IgM secretion, we conducted BM transfer experiments in which we transferred either entire BM or BM depleted of IgM-expressing cells into lethally irradiated RAG-1−/− mice. The results showed that IgM-expressing B cells contained all spontaneous IgM-secreting cells. None (n = 7) of the RAG-1−/− host mice that received surface IgM-depleted BM cells had any measurable serum IgM 6 weeks after transfer. In contrast, all mice (n = 8) that received complete BM had significant donor-derived IgM serum levels (Fig. 4E). Collectively, the data demonstrate the presence of a novel population of B-1 cells in the BM that spontaneously produces natural IgM and significantly contributes to steady-state serum IgM levels. We aimed to further characterize the BM B-1 cells and to compare these spontaneous natural IgM-secreting cells with resting B-2 cells, identified as CD19+ B220+ IgMlo IgDhi and classical B220lo CD43+ CD138+ plasma cells (Supporting Information Fig. 2). The latter were induced in mediastinal lymph nodes via infection of mice with influenza virus A/Mem71 for 10 days.

[28] Future strategies will include regional, national, international exchanges, list exchange, three-way, domino chain and non-simultaneous KTx. A regional KPD Pilot Program, involving adjoining/coordinating transplant centre should be implemented before establishment of national KPD program.[29] KPD using virtual crossmatch is a valid and effective solution selleck screening library for highly sensitized recipients.[30]

Poverty, paucity of RRT facilities in the government sector and high costs in private sector render the majority of ESKD patients unable to access RRT. The solutions to these problems are alleviating poverty, educating the general population, and expanding the transplant programs in public sector Selleck GDC-0980 hospitals. KPD is viable, legal, rapidly growing modality for facilitating LDKTx for patients who are incompatible with their healthy, willing LD. KPD does not require extra infrastructure and facilities. It avoids transplant tourism and commercial trafficking. Transplant centres should work together towards a national KPD program and frame a uniform acceptable allocation policy. The transplant community must act now to remove barriers to a broader implementation of international sharing of KPD lists to further optimize the potential of this modality. “
“Introduction: 

There has been debate as to the value of lower sodium dialysates to control blood pressure in haemodialysis patients, as sodium is predominantly removed by ultrafiltration. Methods:  Re-audit of clinical practice following reduction in dialysate sodium concentration. Results:  Overall dialysate sodium concentration decreased from 138.9 ± 1.7 to 137.8 ± 1.7 mmol/L (mean ± standard deviation),

resulting in a reduction in pre- and post-dialysis mean arterial pressure (MAP) of 4 mmHg (from 100.6 ± 15.6 to 97.1 ± 15.6, P < 0.01 and from 91.7 ± 15.6 Thiamine-diphosphate kinase to 87.1 ± 14.6, P < 0.001 respectively), yet fewer patients were prescribed antihypertensives (49.6 vs 60.6%), and less antihypertensive medications/patient (mean 0.86 vs 1.05), ultrafiltration requirements (2.8% vs 3.2% body weight, P < 0.001), and symptomatic intradialytic hypotension (0.19 vs 0.28 episodes per week, P < 0.001). A multivariable model showed that for a dialysate sodium of 136 mmol/L, younger patients had higher MAP than older patients (0.35 mmHg lower MAP/year older; but with a dialysate sodium of 140 mmol/L, there was minimal association of MAP with age (0.07 mmHg higher MAP/year older). Conclusion:  Change in clinical practice, amounting to a modest reduction in dialysate sodium was associated with a reduction not only in pre- and post-dialysis blood pressures, but also ultrafiltration requirements and symptomatic intradialytic hypotension.

We had expected greater mucosal responses at the highest doses administered here. Even at 1010 CFU, we only detected soluble IgA directed against sonicated L. monocytogenes via the ALS assay; no convincing IgA ELISpot responses were seen. Serum IgA titers directed against the vector were significantly increased overall, although the significance of this finding is uncertain. IgA ELISpots were the best correlates of luminal intestinal (fecal) antibody in earlier assessments of live attenuated Salmonella vaccines where Sorafenib concentration this was carefully studied (37). Systemic humoral immune responses to vector and the foreign antigen were not detected. Although antibodies may play some role

in protection against listeriosis (38), in general, listerial vectors are engineered and studied with the goal of stimulating cellular immunity. All of our volunteers had high baseline antibody titers directed against the nucleoprotein antigen, likely a result of prior influenza infection, which did not change over time. We were somewhat encouraged by an overall statistically significant

increase in IFN-γ spot-forming cells responsive to the complex listerial sonicate antigen, if not the listeriolysin peptides, nor the nucleoprotein antigen as shown graphically in Figure 7. In our and others hands, the listeriolysin peptide pool engendered strong ELISpot responses in mice inoculated parenterally with L. monocytogenes expressing listeriolysin. It was expected that these LLO peptides would be strong, sensitive and specific BAY 80-6946 cell line test peptides in humans, which proved to be incorrect. Our data suggest that humans may preferentially respond to other listerial antigens. We had hoped that existing and measureable IFN-γ ELISpot immune responses to influenza nucleoprotein peptides would be “boosted” by presentation of the nucleoprotein by a live listerial vector, but this could

not be demonstrated. Based upon our ELISpot and ELISA data, virtually all volunteers had strong existing immune responses to the nucleoprotein. In retrospect, Edoxaban perhaps an antigen to which humans are naïve might have presented a lower bar with which to evaluate these vectors. It is possible that we might have detected greater cellular responses to both vector and heterologous antigens by using more sophisticated T-cell studies with re-stimulation in vitro, but we doubt such results would be clinically meaningful. In summary, oral administration of these two vaccine organisms resulted in modest mucosal and cellular immune responses to a complex listerial antigen, but not to a secreted viral foreign antigen. The strains were comparable, immunologically. In our prior study, there were more robust mucosal and humoral immune responses to both sonicated L. monocytogenes and LLO in subjects receiving 109 CFU of the BMB72 parental strain orally. We had hoped that higher doses and improved peptide reagents would allow us to detect cellular responses, but this was not the case.

For instance, in dialysis patients with depression, elevated levels of interleukin-6 have been associated with increased risk of cardiovascular mortality.[43] This inflammatory status may also exist in earlier stages of CKD and contribute to disease progression. The adverse effects of depression on CVD may also be mediated via platelet mechanisms. For example, patients with major depression have consistently been shown to exhibit alterations of multiple platelet parameters involving dysregulation of serotonin secretion. Altered serotonin levels in depressed 5-Fluoracil patients with ensuing platelet activation leading to coronary events have also been observed.[44] The clustering of certain risk factors implicated

in metabolic Selleck Opaganib syndrome (visceral obesity, dyslipidaemia, hyperglycaemia, and hypertension) may also mediate associations between depression and increased CVD risk.[45] Other mechanisms involve adverse health behaviours (e.g. reduced physical activity, smoking, alcohol consumption, excessive eating and poor nutrition), non-adherence to medical treatment and poor utilization of health services. For example, dialysis patients with depressive symptoms have been found to exhibit decreased behavioural

compliance involving diet and interdialytic weight gain, which in turn predicted decreased survival.[29] Further, perception of social resources have been found to influence decision making in regards to uptake and choice of home or in-centre dialysis treatment in people DCLK1 with CKD.[46] Given the increasing prevalence and costs of RRT, interventions that prevent or delay the progression of CKD are crucial. Interventions targeting psychosocial and behavioural risk factors may be a viable alternative to pharmacotherapy in people already receiving multiple medications. There is evidence that non-pharmacological interventions have the capacity to improve depressive symptoms, HRQOL, treatment compliance, physical functioning and reduce CVD risk across various chronic diseases.[3, 47] For example, interventions targeting psychological well-being

have demonstrated positive effects on functional disability, coping skills, self-efficacy and depressive symptoms in people with inflammatory disease,[48] indicating a possible pathway by which similar interventions may be beneficial in people with CKD. Several studies now indicate improvements in depressive symptoms in dialysis patients treated with cognitive behavioural therapy and exercise therapy.[49] Limited data also indicate that behaviour modification may have positive effects on exercise behaviour, fatigue and depressive symptoms in non-dialysed CKD patients.[50] While preliminary, these studies highlight the need for large-scale trials to evaluate the efficacy of non-pharmacological interventions as an adjunct to conventional medical management.

Increased level of this cytokine might reflect the mechanism of limiting the inflammation in the stable phase of disease in our patients. The participation of adiponectin in the resolution of inflammatory reaction is in accordance with the theory presented by Hodge et al. They supported an impaired clearance of the products of apoptosis and cytotoxic reactions, mentioned as important in the pathogenesis of

COPD [7, 23, 24]. The elements of autoimmunity seem to be strictly connected with this theory. The possible autoantigens include: elastin, peptides and immunoglobulins [10, 12], however, whether autoantigen is primary etiologic agent or product of tissue cytotoxic reactions and damage remains unresolved [36]. The role of tobacco smoke in this process is unclear. We did not find AZD4547 supplier any significant differences between smokers and non-smokers and between current smokers and ex-smokers. When we compared the group of never smokers with COPD with healthy never smokers we still observed Nutlin-3 price the significant differences in the proportion of cells described above. There were any correlation of the proportion of CD4+/CD25+ cells with pack/years smoked. This observation could be in agreement with the

notion of genetic predisposition to COPD and only inducible role of tobacco smoke and the persistence of inflammation after smoking cessation in COPD [37, 38]. In conclusion we supported the possible role of CD4+/CD25+ cells in systemic inflammation in COPD. While the deficit of CD4+/CD25+ and CD25high cells may be a primary alteration, the increase of CTLA4 expression and elevated concentration of adiponectin may be a secondary and compensative mechanism. The authors thank Dr Marta Maskey-Warzechowska for her technical assistance in preparing this manuscript. “
“In order to build a common data pool and estimate the disease burden of primary immunodeficiencies (PID) in Europe, the European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This database is a platform for epidemiological

analyses as well as the Suplatast tosilate development of new diagnostic and therapeutic strategies and the identification of novel disease-associated genes. Since its start in 2004, 13 708 patients from 41 countries have been documented in the ESID database. Common variable immunodeficiency (CVID) represents the most common entity with 2880 patients or 21% of all entries, followed by selective immunoglobulin A (sIgA) deficiency (1424 patients, 10·4%). The total documented prevalence of PID is highest in France, with five patients per 100 000 inhabitants. The highest documented prevalence for a single disease is 1·3 per 100 000 inhabitants for sIgA deficiency in Hungary. The highest reported incidence of PID per 100 000 live births was 16·2 for the period 1999–2002 in France. The highest reported incidence rate for a single disease was 6·7 for sIgA deficiency in Spain for the period 1999–2002.

The intracellular replication

and simultaneous dissemination of the pathogen occur prior to the development of the adaptive immune responses. This shows the selleck inhibitor unique feature of M. tb to establish a protected niche where they can avoid elimination by the immune system and persist for ever [4, 5]. The innate immune system has various pathogen recognition receptors (PRRs) that are expressed on the cell surface, in intracellular compartments, or secreted into the blood stream and tissue fluids [6], which specifically recognizes the pathogen-associated molecular patterns (PAMP) for initiating and coordinating the host innate immune response [7]. As per the recent research on PRRs like Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs) and other C-type lectin receptors plays an important role in the recognition of M. tb. Here, we have summarized the information available on host innate immune response especially TLRs, host–pathogen interaction and the

importance of signal transduction mechanisms involved in the pathogenesis of TB. TLRs are phylogenetically conserved mediators of innate immunity, which are essential for microbial recognition on macrophages and DCs [8-10]. Toll was first identified in Drosophila as a type I transmembrane receptor, which controls dorsal–ventral AZD1208 polarity during embryogenesis [11]. After the identification of Toll as an essential receptor in the innate immune

recognition in Drosophila, a homology search of databases lead to the discovery of a homologue of Toll in humans [9]. It is now designated as TLR4 and is involved in the gene expression of inflammatory cytokines and costimulatory molecules [9]. Later studies identified several proteins that are structurally related to TLR4. Currently, 11 mammalian TLRs Chlormezanone were identified of which TLR1-10 are functional in humans. TLRs are transmembrane proteins containing lucine-rich repeats (LRR) in their extracellular domains. The cytoplasmic domain of TLR is homologous to the signalling domain of Interleukin-1 receptor (IL-1R) known as Toll/IL-1 (TIR) domain that links to IL-1R-associated kinase (IRAK), a serine kinase that activates transcription factors like nuclear transcription factor (NF)-κB, which leads to the production of cytokines. Activation of TLR by its specific ligand may result in several possible biological outcomes, ranging from the cytokine secretion, modulation of the adaptive immune response, rapid cellular differentiation, apoptosis and direct antimicrobial activity [12-14]. Of 10 TLRs, TLR1, TLR2, TLR4, TLR6, TLR8 and TLR9 are thought to be involved in the recognition of mycobacteria. Most important M. tb cell-surface ligands that interact with TLRs and other receptors are 19- and 27-kDa lipoproteins, 38-kDa glycolipoprotein, the lipomannan (LM) and mannose-capped lipoarabinomannan (ManLAM) [15-17].

However, Annunziato et al. [43] showed that significant proportions of CD4+ T cells from the gut of patients with Crohn’s disease coexpressed IFN-γ and IL-17. The discrepancy between studies might be because of the differences in specific T cell subsets activating in different disease backgrounds. We identified that both IL-22- and IL-17-producing CD4+ T cells were central memory cells with a phenotype

of CD45RA−CD62L−CCR7+CD27+. Central memory MG132 cells were thought to be long-lived populations, able to expand extensively for an effective secondary immune response. This contrasted with the effector memory phenotype found on IFN-γ-producing CD4+ or γδ T cells, which was CD45RA−CD62L−CCR7− [42, 44]. Taken together, our results suggested that IL-22- or IL-17-producing cells in pleural fluid were long-lived populations with the potential to contribute to long-lasting protection against TB. Elucidating

the mechanisms by which these T cell subsets might control M. tuberculosis infection is the subject of ongoing research. In conclusion, our findings of M. tuberculosis-specific IFN-γ-, IL-22- and IL-17-producing cells in tubercular pleural fluid may reflect the activation of a local protective immune response. The understanding of human local immune responses to M. tuberculosis may facilitate the evaluation of the efficacy of new anti-TB vaccines. buy RAD001 selleck chemical Further investigations may unravel the critical targets for therapeutic intervention in chronic inflammatory diseases. This work was supported by grant 115 (No. 2008ZX10003-011); National Nature Science Foundation of China (No. 30872300) and National Key Basic Research Program

of China (973; No. 2007CB512404). The authors declare no financial or commercial conflict of interest. “
“The relative roles that ageing and lifelong cytomegalovirus (CMV) infection have in shaping naive and memory CD4+ T-cell repertoires in healthy older people is unclear. Using multiple linear regression analysis we found that age itself is a stronger predictor than CMV seropositivity for the decrease in CD45RA+ CD27+ CD4+ T cells over time. In contrast, the increase in CD45RA− CD27− and CD45RA+ CD27− CD4+ T cells is almost exclusively the result of CMV seropositivity, with age alone having no significant effect. Furthermore, the majority of the CD45RA− CD27− and CD45RA+ CD27− CD4+ T cells in CMV-seropositive donors are specific for this virus. CD45RA+ CD27− CD4+ T cells have significantly reduced CD28, interleukin-7 receptor α (IL-7Rα) and Bcl-2 expression, Akt (ser473) phosphorylation and reduced ability to survive after T-cell receptor activation compared with the other T-cell subsets in the same donors. Despite this, the CD45RA+ CD27− subset is as multifunctional as the CD45RA− CD27+ and CD45RA− CD27− CD4+ T-cell subsets, indicating that they are not an exhausted population.

How CD23 on B cells modulates active systemic anaphylaxis needs further BTK inhibitor studies. A direct effect of CD23 on effector cells or a proposed negative regulatory function of CD23 on B cells could be involved [23, 31]. Because the CD23−/− IgE knock-in mice displayed increased anaphylaxis, we reasoned that they would be better targets to test a potential protective effect of basophil depletion on active anaphylaxis. Therefore, we treated sensitized mice with Ba103 Ab (anti-CD200R3), which depletes basophils, but not mast cells [32] to examine the effect on IgE or IgG1 dominated anaphylaxis.

In WT, heterozygous and homozygous IgEki mice 65, 80, and 85% of basophils (CD49b+-IgE+) in peripheral blood were depleted, respectively (Supporting Information Fig. 2). The depletion of basophils resulted in reduction of body temperature drop in all three genotypes. This effect was most prominent in IgE knock-in mice in the late phase of anaphylaxis, between 60–90 min. At the endpoint after 90 min the body temperature was 3–4°C lower in untreated mice as compared with that of basophil-depleted mice. In line with this observation, the mortality rate dropped to zero in treated mice. However, at the peak of anaphylaxis around 30–40 min past challenge, basophil-depleted IgE knock-in mice also reacted with substantial anaphylaxis,

although they recovered faster than the untreated mice (Fig. 4B and C, panels 3 and 4). Due to genetic differences between BALB/c mice (where the knock-in was made) and C57BL/6 mice (used for backcrosses) the IgEki/ki mice express the IgG2a isotype, whereas the WT littermates express IgG2c [33]. This feature of the genetic GDC-0973 research buy manipulation is not due to insufficient backcrossing, but results from the close linkage of the IgG isotypes in the immunoglobulin locus. A contribution of differentially expressed antigen-specific IgG2a versus IgG2c (Fig. 3B and C) to the anaphylaxis phenotype, Amino acid or the moderately increased IgG2b in CD23-competent IgE knock-in (Fig. 3B) is unlikely, because in mice immunized with alum as adjuvant, specific IgG1 is the dominating IgG isotype, resulting in reduced antigen-specific IgG in the IgE knock-in mice

[34]. In summary, IgE-sensitized basophils are most likely responsible for the severe body temperature drop in the late phase of anaphylaxis and contribute to death due to anaphylaxis. However, in the early phase of anaphylaxis, sensitized mast cells do have an important contribution in IgE-dominated systemic anaphylaxis. This is supported by the detection of significantly increased mouse mast cell protease 1 (Mmcp1) in IgEwt/ki mice, but not in IgEki/ki mice (Fig. 4D). Mmcp1 has been identified as a marker that distinguishes IgE- from IgG-mediated anaphylaxis [7]. As basophils do not express this protease, whereas mast cells do – albeit weakly – [35], this suggests that mast-cell degranulation via IgE may partially contribute to the anaphylaxis phenotype.