Although

we found that Lgals3−/− TREG cells produce higher amounts of IL-10 than WT TREG cells that could influence susceptibility to L. major infection, we cannot rule out the possibility that this endogenous lectin could also influence IL-10 production by other immune cells, including macrophages or B cells. This effect Torin 1 in vitro is important given recent studies showing the role of IL-10-producing B cells in controlling susceptibility to L. major infection [37]. Moreover, we previously found that macrophages from Lgals3−/– mice produce higher amounts of IL-10 in comparison with WT mice [7], suggesting that IL-10 may serve as a general effector target of the immunoregulatory activity of galectin-3. These results raise the question of whether galectin-3 could play a pivotal role in controlling IL-10 gene transcription and ultimately limiting TREG cell functionality. Our findings add to the recently documented role of galectin-3 in modulating the severity of L. major infection by facilitating neutrophil recruitment to sites of infection [38]. Thus, distinct galectin-3-regulated mechanisms may dictate susceptibility to L. major infection. Notch receptors and their ligands are important factors that contribute to the generation, expansion,

and function of TREG cells [22]. Notch-3 expression is a hallmark of TREG cells and Notch-3-mediated signaling positively regulates the expansion of TREG cells [39]. We found that Notch-1 and Notch-3 receptors Z-VAD-FMK are differentially expressed on TREG cells from WT versus Lgals3−/− mice. Surprisingly, in our model,

Notch-3 expression was found to be downregulated in TREG cells from infected Lgals3−/− mice. Despite this fact, we detected high levels of Tyrosine-protein kinase BLK Hes-1 transcripts in Lgals3−/− mice, suggesting a more pronounced activation of this pathway. In fact, Anastasi et al. [39] showed that transgenic mice overexpressing the active intracellular domain of Notch-3 display increased accumulation of TREG cells in lymphoid organs and increased expression of IL-10. Activation of Notch signaling directly affects TREG-cell function by regulating Foxp3 expression through RBP-J- and Hes1-dependent mechanisms [40, 41]. In addition, recent reports show that Notch signaling regulates IL-10 production by Th1 cells through a STAT4-dependent mechanism that converts pro-inflammatory Th1 cells into T cells with regulatory activity [42]. These observations led us to propose that increased IL-10 production in Lgals3−/− mice during infection was, at least in part, associated with higher activation of Notch signaling in these cells. This hypothesis has been confirmed by the fact that in vitro differentiated TREG cells from Lgals3−/− mice produced more IL-10 and were more resistant to inhibition of the Notch pathway.

As discussed in the following paragraph, LXR activation following the phagocytosis of apoptotic

cells could be involved in the generation and maintenance of tumor-specific T-cell tolerance (Fig. 1A) [20, 21]. LXR signaling has also been shown to maintain homeostatic levels of neutrophils. Indeed, aged neutrophils are cleared from the circulation www.selleckchem.com/products/3-methyladenine.html by resident APCs through the transduction of “eat-me” signals that upregulate LXR-dependent transcription of Mertk and its partner Gas6 [22]. Altogether, these results suggest that LXRα, LXRβ, or both isoforms control various biologic functions of mouse macrophages and DCs depending on the pathophysiologic context. For instance, the exposure of macrophages and DCs to oxysterols Talazoparib solubility dmso concomitantly to the engagement of TLRs or the exposure to cytokines/growth factors seems to mainly induce an LXRα-mediated activity,

whereas in steady-state conditions, LXRα/β-mediated activity would take place [10, 17, 19]. LXRα has been implicated in the regulation of some functions of human monocyte-derived DCs. During the differentiation of human DCs from circulating monocytes there is a marked upregulation of LXRα transcripts, whereas LXRβ expression is maintained at very low levels [23]. LXRα activation during the differentiation of monocyte-derived DCs blocks the expression of the actin-bundling protein fascin, thereby interfering with immune synapse formation [23].

This ultimately diminishes the T-cell stimulatory ability of maturing monocyte-derived DCs with activated LXRs. Similarly, LXRα activation during DC maturation inhibits the expression of the chemokine receptor CCR7 and, therefore, impairs Phosphoprotein phosphatase DC migration toward the chemokine CCL19 [10, 24, 25]. LXRα silencing in DCs partly abrogates CCR7 downregulation by oxysterols, indicating that in conditions where DCs are activated by inflammatory or bacterial-derived stimuli (i.e., LPS), oxysterols seem to mainly engage and activate DCs via the LXRα isoform. This has also been confirmed by a recent report demonstrating that Prostaglandin E2, which has been shown to license monocyte-derived DCs to express functional CCR7 receptors [26], downregulates LXRα but not LXRβ expression in monocyte-derived DCs as well as in ex vivo purified DCs, thus enhancing CCR7 expression and DC migration toward CCL21 [25] and highlighting the context-dependent outcomes of LXRα and LXRβ activation. Interestingly, Feig et al. have recently shown that in a different stage of DC differentiation (i.e., immature DCs), LXR ligands induce CCR7 expression, a function dependent on the activation of both LXRα and -β isoforms [27]. Therefore, oxysterols exert opposite effects on the expression of CCR7 depending on the stage of DC differentiation (immature versus maturing DCs), possibly through the differential activation of LXRα and/or LXRβ isoforms.

In the peritoneal cavity of secondarily infected mice (i.p. inoculation of metacestode vesicles), the larval parasite interacts with the environmental cells including particularly DCs. These cells

are the most important antigen-presenting cells (APCs), distributed in the periphery as sentinel cells that can rapidly interact with nonself antigens. They represent the link between innate and adaptive immune response (25). It has been widely reported that mainly DCs initiate and influence the orientation (Th1 or Th2) of the immune response (26). Beside these functions, it has been found in many helminthiases that DCs played a crucial role in the modulation of peripheral immune tolerance and in the induction of suppressive T-cell activation (27). DC function appears to become selleck kinase inhibitor itself modulated see more during helminthic infection, which results in a mutual benefit for the host and the parasite (28). Investigating what happens in vivo to the peri-parasitic pe-DCs will help us to understand the subsequently developing E. multilocularis-induced host immune response and might explain how pe-DCs

participate in the survival strategy of the parasite. A priori we have found that the percentage of pe-DCs increased twice in AE-infected mice in comparison with naive control mice, indicating an important recruitment of such cells to the site of infection. In the context now of an intraperitoneal AE-infection, we expected that in the immunological environment of the peritoneal cavity, characterized by the high expression levels of IL-4 and TGF-β, NK cells, whenever, migrate to the site of infection and www.selleck.co.jp/products/azd9291.html will not undergo any modification regarding the

expression of co-stimulatory molecules. It is known that IL-10 and to a lesser extent TGF-β down-regulate the expression of the co-stimulatory molecules CD80, CD86 and CD40. Moreover, the cytotoxic activity of NK cells is also weakly inhibited by TGF-β. Thus, the presence of NK and even myeloid precursors in the peritoneal cavity of AE-infected mice should not interfere with the analysis by flow cytometry of co-stimulatory molecules on the surface of CD11c+ cells such as AE-pe-DCs. Nevertheless, NK cells may contribute to the reduction of co-stimulatory molecules on the surface of AE-pe-DCs because in certain conditions, these cells may produce IL-4 and latent TGF-β. Such NK cells could thus be potential co-players in the establishment of Th2 responses in chronic helminthic infections. Although the involvement of NK cells in the described effects on the CD11c+ compartment of our experiments is not very likely, the role of these cells in the peritoneal cavity of AE-infected mice will nevertheless merit further studies. The local cytokine environments and pathogen components are the main factors that influence DC activation and subsequently polarization of immune responses (29,30). Pe-DC activation was first analysed upon gene expression levels of selected cytokines.

At baseline, the two groups in any measured clinical information were comparable. The primary endpoint (doubling serum creatinine) showed no significant difference between the two groups during 3-year follow-up. The secondary endpoint (50% reduction in 24-h urinary protein) occurred in 23 patients in the treatment group and 20 patients in the control group. The time to the secondary end-point was shorter in the treatment group than the control group (8.13

months vs 19.63 months, P = 0.019). However, at the 3-year follow-up, the 24-h urinary protein levels were not significantly different Kinase Inhibitor Library in vitro from the baseline levels (P = 0.99 and P = 0.66, respectively). At the 1-year follow-up, plasma cholesterol in the treatment group was markedly lower than in the control group (4.12 ± 1.28 vs 5.03 ± 1.01, P = 0.02). Kidney function remained stable and there was no significant difference in two group patients. Probucol combined with valsartan led to a more rapid decrease of 24-h urinary protein excretion than valsartan alone.

However, the long-term effect needs further investigation. Immunoglobulin A (IgA) nephropathy is the most common primary glomerular disease and is a major cause of end stage renal disease (ESRD).[1, 2] The pathogenesis of IgA nephropathy is still poorly understood,[3, 4] and although some treatments are available, their renoprotective effects are not sufficient to prevent the development of IgA nephropathy to ESRD.[4, 5] Therefore, it will be necessary to develop new drugs for IgA nephropathy based on a Atezolizumab manufacturer new mechanism of action. Clinical studies and animal experiments indicate that activation of the renin-angiotensin system (RAS) plays an important role in the progression of IgA nephropathy.[6] Studies that used short term follow-ups indicated that RAS inhibitors can reduce excretion of urinary protein and 3-mercaptopyruvate sulfurtransferase protect kidney function in patients with IgA nephropathy. Recently, accumulating evidence suggests that patients with IgA nephropathy are under oxidative stress due to the activation of oxygen

free radicals, with increases in reactive oxygen species (ROS) and elevation of serum superoxide dismutase (SOD).[7-9] This damages renal glomeruli, activates mesangial cells to secrete transforming growth factor-β (TGF-β) and extracellular matrix, and results in disease progression.[7] Moreover, increased levels of a marker of oxidative stress, advanced oxidation protein products (AOPPs), have been reported to be significantly associated with proteinuria and disease progression in patients with IgAN.[10] The role of the oxidative milieu as a risk factor for progression of IgAN as well as for mortality has recently also been supported by the association with the polymorphism in the promoter region of the hemeoxygenase-1.

T cell autoreactivity in peripheral blood of patients can serve as a surrogate marker of ongoing insulitis [2,3], but detection of circulating islet autoreactive

T cells is hampered by low precursor frequencies and possibly regulatory T cells [4–8]. It is unclear to what extent peripheral T cell autoreactivity bears relevance to the pathogenesis of type 1 diabetes. Studies to identify diabetes-associated T cells in men have been hindered thus far by the inaccessibility of the insulitic lesions. In both humans and the non-obese diabetic (NOD) mouse strain, that develops Angiogenesis inhibitor autoimmune diabetes spontaneously, β cell destruction is preceded by leucocyte infiltration of the pancreatic islets (insulitis). We have demonstrated recently that T cells isolated from peripheral blood of prediabetic subjects and reactive against the islet autoantigen glutamic acid decarboxylase 65 (GAD65) home to pancreatic tissue and pancreas-draining lymph nodes but not to other secondary lymphoid tissues when injected into NOD/severe combined immunodeficiency (SCID) mice

[9]. This process was dependent upon co-injection of check details human leucocyte antigen (HLA)-matched antigen-presenting cells and the relevant autoantigenic epitope and was amplified by β cell distress following pretreatment of recipient mice with low-dose streptozotocin. These data imply that islet autoreactive T cells isolated from the circulation of (pre)diabetic subjects may bear relevance to insulitis and possibly to the β cell

destruction process. Kent et al. have described oligoclonality of CD4 T cells in the pancreas-draining lymph nodes of two long-standing type 1 diabetes patients [10]. This report was MycoClean Mycoplasma Removal Kit the first to describe immune phenotype and reactivity in draining lymphoid tissue that may reflect autoimmune reactivities associated with the type 1 diabetic lesion, albeit that in the two reported cases, both insulitis and target β cells were lacking. The authors suggested further that some of these T cells responded to insulin peptide. While there is compelling evidence that insulin serves as a major autoantigen in animal models of type 1 diabetes [11–14], similar evidence of immunodominant T cell responses to insulin, rather than other candidate islet autoantigens, in clinical type 1 diabetes is circumstantial [6,15,16]. Nevertheless, this seminal study set the stage for studies on T cell autoreactivity in pancreas-associated tissues. In this study we present four cases where whole pancreas and some pancreas-draining lymph nodes were obtained from recent-onset type 1 diabetic patients, including one case of viral infection of pancreatic β cells. Two of these patients died accidentally, the other two died of brain oedema as a complication of diabetic ketoacidosis.

Methods: Systolic blood pressure(SBP) was measured at 1-week intervals after clipping. Two and 5 weeks after operation, the rats were sacrificed for western-blot and immunohistochemistry. Results: SBP increased in 2K1C rats(n = 12) within 1 week after unilateral renal clipping relative to sham rats(n = 8). Glomerulosclerosis and tubulointerstitial inflammation were aggravated in maintenance phase. From the acute phase, CK showed significant reduction

in ACE2, leading to an increased ratio of ACE/ACE2. Juxtaglomerular(JG) renin was increased in CK and suppressed in NCK, but collecting duct(CD) renin was enhanced in both kidneys selleck inhibitor in immunohistochemistry. In the maintenance phase, medulla in both kidneys presented significantly increased ACE and decreased ACE2, along with up-regulation of renin in medulla of NCK. Immunohistochemistry revealed more intense CD renin staining in both kidneys. Simultaneously AT1R in CK cortex was not suppressed, albeit there was reduced MasR, thus AT1R/MasR ratio was insignificantly elevated in cortex. Conclusion: Even though the reduction of ACE2 along with increase of JG renin in CK could initiate hypertension in the acute phase, eventually a higher stimulation of ACE and suppression of ACE2, according to the activation of CD renin in NCK, are HSP inhibitor thought to play key roles for keeping hypertension during

the maintenance phase. In addition, we cautiously presumed the imbalance of AT1R and MasR might have some effects to hypertension in this model. KATSUNO TAKAYUKI, YAMAGUCHI MAKOTO, Edoxaban TANAKA AKIHITO, YASUDA YOSHINARI, KATO SAWAKO, SATO WAICHI, TSUBOI NAOTAKE, ITO YASUHIKO, MARUYAMA SHOICHI, MATSUO SEIICHI Department of Nephrology, Nagoya University Graduate

School of Medicine Introduction: Albuminuria is known to be a predictive factor for chronic kidney disease (CKD) and cardiovascular disease (CVD). Particularly in the hypertensive patients, albuminuria increases the risk of CKD and CVD. However, little is known about the prevalence of albuminuria among hypertensive patients. The aim of this study is to conduct factual investigation of albuminuria. Methods: The study subjects were 387 individuals who attended a private practice as an outpatient. Semi-quantitative measurement of urinary albumin excretion corrected for the urinary creatinine levels (albumin creatinine ratio: ACR) was conducted by using a urine reagent paper in the hypertensive patients, and cross-sectional analysis was performed. Results: The cohort consisted of 215 males (55.6%) and 172 females (44.4%), with a mean age of 68.3 years (range 28 to 92 years). 367 patients (94.8%) used an antihypertensive agent. 155 patients (40.1%) had a diabetes mellitus. In 57 patients (14.7%) tested, there was evidence of proteinuria by using a test strip. Mean serum creatinine for the entire cohort was 0.83 mg/dL (range 0.4 to 2.1 mg/dL). Among 385 patients, 197 (51.

S2b). The frequency of these two subsets among cDC in MLN of CD47−/− and WT mice did not differ significantly (Fig. S2c). CD11c+ MHC-IIbright cells could be further separated into two subsets based Angiogenesis antagonist on their co-expression of CD11b and the CD47 ligand CD172a (Fig. S2d). Expression of CD172a by CD11b+ DC was also confirmed in other tissues of GALT (for PP, Fig. S3d). Analysis of multiple mice revealed a significant reduction in the frequency of CD103+ CD11b+ CD172a+ MLN cDC in CD47−/− mice compared with WT mice (Fig. 1c). CD103− cDC were further divided based on their mutually exclusive expression of CD8 and CD11b (Fig. S2e). Comparison of these populations

showed a significant reduction in the frequency of CD103− CD11b+ CD8− cDC in CD47−/− mice compared with WT mice (Fig. 1d). Small intestinal LP CD11c+ MHC-II+

cells were next analysed for CD103 expression (see supplementary material, Fig. S3a,b). The frequency of CD103− cells, which all expressed CD11b, was significantly reduced in CD47−/− mice (42 ± 15% in CD47−/− mice versus 55 ± 11% in WT, P < 0·05). When the CD103+ population was further divided into CD8+ CD11b− and CD11b+ CD8− cells (Fig. S3a; right panels), we found that the frequency of the latter cDC population was also significantly reduced in CD47−/− mice (Fig. 1e). These differences were not the result of an Alvelestat increase in CD103+ or CD103+ CD8+ CD11b− cDC, because the frequency of total CD11c+ MHC-II+ cells in LP did not differ between CD47−/− and WT mice (Fig. 1a). Immunohistochemical staining showed no apparent difference in the localization of CD11c+ cells in the small intestinal LP, but suggested a decrease of CD11c+ CD103+ CD11b+ (white) cells in CD47−/− mice, compared with WT mice (Fig. S3c). In contrast to our findings in MLN and LP, CD47−/− mice had a normal frequency of CD11b+ cDC in PP (Fig. 1f and Fig. S3d), and a normal distribution of this population

in the subepithelial dome region (Fig. S3e), when compared with WT mice. These results show that CD47−/− Baricitinib mice have a reduced frequency of cDC in MLN, but not in LP or PP, compared with WT mice. Moreover, while DC subsets are unaltered in PP of CD47−/− mice, a specific decrease of CD11b+ cDC is apparent in LP and MLN. After observing GALT-specific lymphopenia and subset-specific defects in LP and MLN cDC of CD47−/− mice, we next assessed CD4+ T cell activation in the GALT of these mice after oral immunization. CFSE-labelled OVA-transgenic (DO11.10) CD4+ T cells were adoptively transferred to CD47−/− and WT mice. The use of CD47+ DO11.10 T cells eliminated possible intrinsic defects in responding T cells. After confirming that mesenteric lymphadenectomy completely abrogates oral tolerance induction in mice fed 50 mg OVA (see supplementary material, Fig. S4a), but that it does not reduce the generation of intestinal or serum anti-OVA IgA and IgG in mice fed OVA + CT (Fig.

It is therefore likely that IL-4R-α expression on airway epithelium might represent an important feedback mechanism through which IL-4 and IL-13-secreting immune cells enhance

Th2-cell immunity in ongoing immune responses. Interleukin 1α and IL-1β are among the first described members of the prototypical IL-1 cytokine family that also includes IL-18, IL-33 (IL-1F11), and many others. IL-1β is synthesized as a proform that requires cleavage via the inflammasome-caspase-1 axis to be secreted as a biologically active cytokine. There is renewed interest in the role of IL-1 and related cytokine family members in promoting asthmatic airway inflammation, due to new evidence in HDM-driven models of asthma, as well as to genetic polymorphism studies in human cells [45]. Indeed, initially it was thought that IL-1 played only a minor role https://www.selleckchem.com/products/ink128.html in asthma, as symptoms in the classical OVA-alum model of asthma were not reduced in IL-1R-deficient mice. [46, 47]. Using radiation-induced bone marrow chimeric mice and exploiting the natural route of pulmonary exposure to HDM allergen, we have recently found that IL-1R triggering on radioresistant PCI-32765 ic50 lung epithelial cells promotes the innate immune response to natural allergen [41]. Autocrine release of IL-1-α by HDM-exposed bronchial

epithelial cells leads to TSLP, GM-CSF, and IL-33 production by epithelial cells, and IL-1α is required for the development of Th2 immunity to HDM in vivo (Fig. 2) [41]. It is still unclear whether the inflammasome-caspase1-IL-1α axis is involved in asthma development as one group failed to see an effect of Nlrp3 deficiency on asthma development in their mouse model whereas other groups found a role when allergens were introduced via the skin or alum was used as an adjuvant [43, 48, 49]. Interleukin-33 has been shown to act upstream of the type-2 effector cytokine cascade, by stimulation of various innate and adaptive immune cells, and by inducing the apoptosis

of lung epithelial cells. Allergic asthma patients express Etoposide supplier higher levels of IL-33, as determined by mucosal biopsies, as compared with those of healthy subjects, and genetic association studies have identified SNPs in the lL-33 and IL-33R (T1/ST2) locus associated with asthma [50, 51]. In mice, neutralization of IL-33 blocks development of lung Th2 immunity to a number of allergens, such as HDM and peanuts, as well as to lung-dwelling parasites such as hookworms [41, 52, 53]. Numerous cells of the innate immune system, such as DCs, macrophages, basophils, mast cells, and eosinophils express T1/ST2 (the receptor for IL-33) and stimulation of these cells by IL-33 leads to prolonged survival and/or activation, often leading to increased Th2 immunity in mouse models of allergy and asthma [50, 52, 54-57]. Little is known, however, about the mechanism of IL-33 release from epithelial cells, endothelial cells, fibroblasts, and immune cells [58].

23 It has recently been shown that the assumption of Guyton, namely, that a positive salt balance raises blood pressure by the intermediate step of expanding the extracellular volume, is a simplification. Recent work of Machnik24 showed that sodium retention following high salt intake is partially the result of non-osmotic salt storage in the skin by interaction of the cationic sodium with anionic sulfate groups of skin glycosaminoglycans. More importantly, salt retention by glycosaminoglycans in the skin activates tonicity-enhancer binding protein (TonEBP) which triggers the synthesis of vascular endothelial growth factor (VEGF)-C, the lymphangiogenesis-inducing MLN0128 isoforms

of VEGF, leading to increased lymph formation. Of note, high VEGF-C concentrations were found in patients with refractory hypertension, illustrating the human relevance of these experimental findings and calling for examination of DAPT ic50 this indicator in patients with refractory hypertension and also patients on dialysis. Guyton had shown that reducing the number of nephrons caused a shift in the pressure natriuresis relationship

to the right, thus indicating that higher blood pressure values were necessary to permit the kidney to achieve equilibrium between ingested and excreted sodium. Animal experiments indicated that neonatal uninephrectomy, namely, nephron loss, caused particularly impressive salt sensitivity of blood pressure.25 The mechanisms conferring salt sensitivity are currently not completely elucidated. High salt intake suppresses the renin–angiotensin

system in the circulation, but paradoxically an increase of tubular fluid angiotensin II is seen on high salt.26 Furthermore, in the presence of a high salt intake, the action of aldosterone is increased. The consequences of this have recently been beautifully illustrated by an animal experiment where the promoter of aldosterone synthase had been manipulated to increase transcription of aldosterone synthase. These animals were normotensive on low salt, but developed hypertension associated with low serum potassium and increased epithelial sodium channel activity on high salt.27 Obviously, high salt intake is a Lepirudin permissive factor for the hypertensinogenic effect of aldosterone. This is illustrated by observations in tribes with extremely low sodium intake (∼1 mmol/day) who have extremely high aldosterone concentrations yet low blood pressure values (102/62 mmHg).28 Interesting observations document that the blood pressure modifying effect of aldosterone does not necessarily require the kidney. Gross29 showed that 50 mg spironolactone lowered blood pressure in anuric haemodialysis patients by 11 mmHg, remarkably without change in serum potassium.

For example, there is a clear size polymorphism in the gene encoding the major sporozoite surface antigen circumsporozite protein (CSP), which indicates sequence variation between these strains (data

not shown). CSP contains both T-cell and B-cell epitopes (26,27), and differences between strains at these domains could result in the strain-specific effects we have observed. Interestingly, it has recently been shown that CSP plays only a minimal role in the protection obtained with live sporozoites under anti-blood stage chemoprophylaxis, indicating Compound Library in vivo the involvement of other, as yet uncharacterized major antigens (28). A future direction of this work is to utilize the strain-specificity of pre-erythrocytic stage immunity apparent between strains of P. c. chabaudi in genetic linkage analyses, including Linkage Group Selection (29), in order to identify these antigens. We thank Les Steven for technical assistance and Sofia Trindade Borges for discussion. This work was supported by The Cunningham Roxadustat mouse Trust of the UK (to R.C), A Royal Society Bilateral Grant for Co-operative Research (to R.C and R.L.C) and a Sasakawa Foundation Butterfield Award (to R.L.C). “
“Experimental

Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, revealing a strong granulomatous response and a low susceptibility to dissemination. Moreover, it has been shown that eosinophils are components Methisazone of the inflammatory response to C. neoformans infections. In this in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of C. neoformans, and that the phenomenon involves the engagement of FcγRII and CD18. Moreover, our results showed that the phagocytosis of opsonized C. neoformans triggers eosinophil activation, as indicated by (i) the up-regulation of major histocompatibility complex

(MHC) class I, MHC class II and costimulatory molecules, and (ii) an increase in interleukin (IL)-12, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production. However, nitric oxide (NO) and hydrogen peroxide (H2O2) synthesis by eosinophils was down-regulated after interaction with C. neoformans. Furthermore, this work demonstrated that CD4+ and CD8+ T lymphocytes isolated from spleens of infected rats and cultured with C. neoformans-pulsed eosinophils proliferate in an MHC class II- and class I-dependent manner, respectively, and produce important amounts of T-helper 1 (Th1) type cytokines, such as TNF-α and IFN-γ, in the absence of T-helper 2 (Th2) cytokine synthesis. In summary, the present study demonstrates that eosinophils act as fungal antigen-presenting cells and suggests that C. neoformans-loaded eosinophils might participate in the adaptive immune response.