In this system, DDA targets the vaccine antigen to APCs while TDB

In this system, DDA targets the vaccine antigen to APCs while TDB provides proinflammatory stimuli, triggering a Th-1 cytokine response via a TLR-independent pathway (Agger et al., 2008). CAF01 has proven to be highly efficacious, inducing cellular and humoral responses simultaneously in animal models more effectively than the single antigens administered alone. In addition to its priming activity, this vaccine has also been demonstrated to have a BCG booster effect (Doherty et al., 2004; Davidsen et al., 2005). AS01B, developed by Corixa

and GlaxoSmithKline Ensartinib solubility dmso Biologicals, contains the TLR4 ligand MPL and the saponin derivative QS-21 in a liposomal formulation including the fusion molecule Mtb72F. The Mtb72F antigen is comprised of the PPE family member Rv1196 inserted into the middle buy PXD101 of the putative serine protease Rv0125, which is thus present as two fragments (Mtb32C–Mtb39–Mtb32N) (Skeiky et al., 2004). In the AS01B or AS02A formulations, this vaccine has also been demonstrated to have priming and BCG booster effects (Brandt et al.,

2004). IC31, also developed by the Statens Serum Institute, consists of a vehicle combining the synthetic antimicrobial peptide KLKL5KLK, which actively loads APCs with antigen, and the immunostimulatory TLR9 ligand ODN1a, with the fusion proteins H1 and Ag85B–TB10.4 (Agger et al., 2006; Lingnau et al., 2007). This vaccine confers protective immunity in murine tuberculosis models and was recently shown to safely induce strong T-cell responses with a mixed Th-1/Th-2 cytokine profile in both neonates and adults (Kamath et al., 2008). CAF01, AS01B and IC31 are currently undergoing clinical Phase I/II trials. Mtb72F/AS01B is being tested in Lausanne, Switzerland, in individuals previously second exposed to BCG or previously treated individuals

currently infected with Mtb. H1 in IC31 and CAF01 are being tested in Leiden, the Netherlands, in purified protein derivative (PPD)-negative subjects. These adjuvants share the same basic combination of a delivery vehicle and a Th-1-skewing immunomodulator, conferring more potent protection against tuberculosis infection than single immunomodulators (CpG or MPL) or delivery vehicles lacking immunomodulators (liposomes or niosomes) (Agger et al., 2006). LTK63, a modified and detoxified heat-labile toxin derived from E. coli, has been combined with the fusion protein H1 for nasal immunization and has passed Phase I clinical trials (in London, UK, with PPD-negative subjects). A strong and sustained Th-1 response mediated by IFN-γ-secreting CD4+ T cells was observed, leading to long-lasting protection against tuberculosis and boosting prior BCG-induced immunity (Dietrich et al., 2006; Badell et al., 2009).

To yield sufficient cells to perform the assays, PBMCs


To yield sufficient cells to perform the assays, PBMCs

from both animals in each group were pooled. All assays were performed in triplicate, with average values and SDs calculated. As a positive control, cells were cultured with concanavalin A (Sigma), which was present at a final concentration of 2.5 μg mL−1. Medium alone was used as a negative control. Plates were incubated in a humid 5% CO2 environment at 37 °C for 96 h, and then pulsed for 18 h with 18.25 KBq (1 μCi) [3H] thymidine (Amersham Biosciences, UK) per well. The cells were harvested using a Packard Filtermate Harvester onto glass fibre filters (Packard, the Netherlands), and activity was counted in a MicroBeta TriLUX direct beta counter (Perkin Elmer). Results were expressed as average counts per minute (±SD). All data were expressed as means±SEM SEs. Statistical significance (P-values) was determined using Student’s t-test. Results were considered significant with P<0.05 and highly HIF inhibitor significant with P<0.01. Figure 1 shows a comparison of HBsAg-specific antibody responses LY2606368 datasheet between the groups of rabbits vaccinated with the phage vaccine, λHBs and the commercial protein vaccine, Engerix B. Rabbits in the phage vaccine group showed significantly higher (P<0.01) responses at days 33,

47, 68 and 82, when compared with the protein-vaccinated group. Additionally, three of the phage-vaccinated rabbits showed a response with an OD >1 after one vaccination and all did

after two vaccinations (Fig. 1c). Only one rabbit in the protein-vaccinated group showed a response >1 OD unit after two vaccinations and it took three vaccinations until four of the five rabbits showed this level of response (Fig. 1b). LSAs were performed on two randomly selected animals from each of the bacteriophage and commercial vaccine groups. PBMCs were extracted as described, pooled for the two animals from each group and stimulated with either recombinant HBsAg or whole phage particles. The results of these LSAs are shown in Fig. 2. The results are plotted as raw counts. The stimulation indices (SIs) were calculated by taking the raw count at a specific time and dividing it by the value from the control (i.e. no antigen) value. Lymphocytes from rabbits vaccinated with either the phage Cyclin-dependent kinase 3 or the commercial vaccines that were then stimulated with recombinant HBsAg antigen both showed an increase in counts, with maximal SIs of 3.45 (phage vaccinated) and 3.20 (protein vaccinated) (Fig. 1b). SIs in cells to which phage were added as a stimulating antigen (Fig. 2b) were significantly higher, reaching 34 in the phage-vaccinated group and 25 in the HBsAg recombinant protein-vaccinated group. The relatively high stimulation index observed in the cells extracted from animals vaccinated with recombinant protein, when stimulated with phage antigen, is due to the nonspecific immunostimulatory properties of the phage preparation.

In both cases, CD161 expression levels appeared lower in NK cells

In both cases, CD161 expression levels appeared lower in NK cells from individuals with symptomatic HCMV infection, an effect that was not perceived when groups were compared (Fig. 1). The NKR distribution pattern associated to HCMV infection in T lymphocytes resembled only partially that observed in NK cells (Fig. 2). Overall, the absolute numbers of NKR+ T cells were increased in HCMV+ children, particularly in the congenital symptomatic group. In fact, the proportions of

NKG2C+, LILRB1+, and CD161+ T cells were significantly higher in congenitally infected than in noninfected children. In addition, NKG2A+ T cells appeared also higher in children with congenital symptomatic infection, at variance with the reduced proportions of NKG2A+ NK cells in the same group. Altogether, these results point Raf inhibitor out that marked changes in NKR distribution, particularly an increase of NKG2C+ and LILRB1+ NK cells, are associated with congenital symptomatic HCMV infection. The putative implications of the NKG2C deletion on the response to HCMV infection are uncertain. On that basis, a genotypic analysis of NKG2C was conducted in children with symptomatic (n = 15) and asymptomatic (n = 11) congenital infection, as well

as in a control group including children with postnatal infection (n Roscovitine concentration = 11) and noninfected (n = 19). The homozygous NKG2C deletion was found in a single uninfected control individual. In addition, no significant differences were found between the frequencies 3-mercaptopyruvate sulfurtransferase of the heterozygous NKG2C+/− genotype detected in uninfected controls and children with congenital infection (42.1% versus 34.6%; p = 0.61). Altogether these results argue against a direct relation of the NKG2C deletion with the incidence of congenital HCMV infection in newborns. In line with previous reports [26, 27, 32], individual differences in NKG2C surface staining intensity were noticed (Supporting Information Fig. 1). The NKG2Cbright/intermediate expression pattern was generally

associated to HCMV infection, whereas all noninfected and ∼43% of infected children displayed a predominant NKG2Cdim phenotype. The proportions of NKG2C+ cells correlated significantly (r = 0.74; p < 0.001) with the KLR surface expression levels (MFI). The possibility that NKG2C copy number might influence the expansion of NKG2C+ cells and/or the expression levels of the receptor was addressed. To this end, the proportions and absolute numbers of NK cells bearing NKG2C, as well as its surface staining intensity, were compared after stratification for HCMV infection and the NKG2C genotype. As expected, increased proportions of NKG2C+ NK cells and higher surface levels of the KLR were detected in HCMV-positive children (Table 3); though less marked, a significant association of both parameters with the NKG2C genotype was also noticed.

The serum concentrations of thyroid hormone, anti-thyroglobulin (

The serum concentrations of thyroid hormone, anti-thyroglobulin (Tg) and anti-thyroperoxidase (TPO) antibodies were measured by chemiluminescent immunoassay (Maglumi 2000 Plus) according to the manufacturer’s protocol. Twenty age- and sex-matched healthy subjects were included as controls. Peripheral blood selleck chemicals samples were obtained from all patients and healthy controls. Thyroid

glands were obtained from six HT patients who were undergoing thyroidectomy. All the patients were positive for Tg-antibody and TPO-antibody and had normal hormone levels, except for one patient (FT4: 7·92 pmol/l). Two of the patients were bilateral goitre; others were unilateral. Lymphocytic infiltration was detected in the goitres. Thyroid tissue from the patient with simple goitre was used as control. Ethical approval was obtained from the Affiliated People’s Hospital of Jiangsu University, and informed consent was obtained from all individuals.

Levels of plasma leptin and CD4+ T cells-derived leptin were measured using a human leptin ELISA immunoassay GDC-0449 concentration (R&D Systems, Minneapolis, MN, USA), following the manufacturer’s protocol. Human peripheral blood mononuclear cells (PBMCs) were isolated by standard density-gradient centrifugation over Ficoll-Hypaque solution. Plasma samples were collected through centrifugation and stored at –80°C for measurement. Human CD4+ T cells were purified from PBMCs Rebamipide by magnetic beads using a CD4+ T Cell Isolation Kit (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany), with purity routinely higher than 95%. CD4+ T cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, 100 U/ml penicillin

and 100 μg/ml streptomycin at 37°C in a humidified atmosphere of 5% CO2. For leptin detection, CD4+ T cells were cultured with anti-human CD3 monoclonal antibody (mAb) (10 μg/ml) and anti-human CD28 mAb (2 μg/ml) for 72 h. Supernatants were then used to detect the levels of leptin by ELISA. For in-vitro blocking experiments, 10 μg/ml human leptin-neutralizing mAb (R&D Systems) was administered in CD4+ T cell culture in the presence of soluble anti-human CD3 mAb (10 μg/ml) and anti-human CD28 mAb (2 μg/ml); the irrelevant isotype-matched antibody was used as control. Thyroid specimens were minced and then digested with collagenase II (Sigma-Aldrich, St Louis, MO, USA) for 1–2 h at 37°C and then isolated by density-gradient centrifugation. Finally, thyroid mononuclear cells (TMCs) were obtained. The viability of cells was found to be higher than 95%.

IV inoculated parasites reach the

IV inoculated parasites reach the liver within minutes (26), whereas sporozoites inoculated into the skin slowly trickle out of the inoculation site over a period of 1–3 h (27). Our results indicate that the lower parasite liver load after ID inoculation is unlikely to be explained by a delayed arrival

of sporozoites in the liver. Comparison of the parasite liver load at 35 h post-ID injection was still ±15 times lower compared to the parasite liver load at 30 h post-IV injection (Figure 2). Despite differences between parasites species, including among others infectivity (28) or host cell preference (29–31), our data in P. berghei parallel previous results in P. yoelii studies (25). Therefore, the relatively low level of parasites capable of reaching the liver after ID injection is likely a common feature among Plasmodium species.

CD8+ T cell responses are known to be essential for protection induced by attenuated live sporozoite immunization in rodent models. Our data corroborate previous studies on P. berghei RAS-induced immunity showing expansion of CD8+ memory T cells, mainly in the liver, together with high IFNγ production in IV immunized SB203580 clinical trial mice (12–15). The low immune responses observed after ID immunization likely follow the low parasite liver load. RAS ID and subcutaneous immunization of human volunteers also show low protection levels, and in nonhuman primates and mice subcutaneous or ID immunization lead to lower Phosphatidylinositol diacylglycerol-lyase IFNγ responses compared to IV sporozoite immunization

(18). Despite the differences in phenotyping and gating strategy, CD8+ effector (memory) T cells (CD44hi CD62L-) and not central memory T cells (CD44hi CD62L+) are identified as induced T-cell subset. In another study using the P. yoelii model, major CD8+ T cell responses were generated in the draining lymph nodes after infected mosquito bites or ID inoculation of sporozoites. Although parasite liver load was reduced, complete protection defined as impediment of blood-stage infection was not evaluated (32). We did not test the regional lymph nodes response and cannot exclude a possible contribution but our data clearly demonstrate that ID inoculation is inefficient in inducing protection. In addition, a measure of sporozoite load in regional lymph nodes following ID inoculation would have been informative. Unfortunately, in vivo visualization of PbGFP-Luccon is not possible because of a relatively low luciferase expression at the sporozoite stage (22). Next to cellular components, antibody responses can contribute to protection by whole sporozoite immunization (8). Our data suggest that induced functional antibodies may contribute to protection but are more likely related to exposure.

Mast cells play a key role in allergic and inflammatory reactions

Mast cells play a key role in allergic and inflammatory reactions. Mast cells and some tumour cell lines such as RBL-2H3 express the high-affinity IgE receptor (FcεRI) on their cell surface. FcεRI is a member of the multichain immune recognition receptors (MIRRs), including T- and B-cell receptor. With regard to OVA-challenged and IgE-mediated mast cell degranulation, FcεRI aggregation activates phospholipase Cγ to increase IP3 generation. The IP3 selleck inhibitor causes Ca2+ release from the endoplasmic reticulum through IP3 receptors, which consequently

results in a large amount of Ca2+ influx via SOCs, leading to mast cell degranulation. In the present study, we demonstrated for the first time that parallel to enhancement of food allergen–induced mast cell degranulation, OVA-mediated Ca2+ entry through SOCs was increased. Given that increasing Ca2+ entry through SOCs enhances mast cell degranulation [20], we conclude that increase in Ca2+ entry through SOCs contributes to food allergen–mediated mast cell degranulation. The two membrane proteins, STIM1 and Orail, have been shown to be essential for the activation of SOCs [16]. Overexpression of Orai1 together with STIM1 has been suggested to upregulate Ca2+ entry through SOCs upon stimulation. In this study, we found that both mRNA and protein expressions levels of Orai1 and

STIM1 in mast cells were increased in OVA-sensitized animals, which is proposed to be an important reason accounting for the increase in SOC-mediated Ca2+ entry and mast cell activation. It has been suggested that the N-terminal Selleck Small molecule library of STIM1 is glycosylated and translocated from endoplasmic reticulum to the cell membrane when the calcium store is depleted, which process is

required for activation of SOCs [30]. This is in line with our study as the translocation of STIM1 protein to activated mast cell membrane in OVA-sensitized mast cells. Therefore, our study demonstrates for the first time that overexpression and activation of SOCs contributes to enhancement of Ca2+ entry through SOCs in food-allergic rats. Activated mast cell can release a diverse array of biologically active products, including preformed granule contents, the de novo synthesis of eicosanoids, Methocarbamol cytokines, chemokines and free radicals (such as ROS) [31]. Large amount of ROS has been demonstrated to generate in inflammatory cells during asthma, but little information is known in the situation of food allergy. A number of studies report that ROS are involved in the signals leading to degranulation and cytokine secretion in mast cells [32, 33]. In this study, we found that ROS production was significantly increased in the peritoneal lavage solution. Using Ebselen to partially scavenge ROS production (mainly hydrogen peroxide), Ca2+ entry through SOCs was inhibited.

Area of necrosis was significantly smaller in primary IP group ve

Area of necrosis was significantly smaller in primary IP group versus

secondary IP group in the absence of global ischemia (P < 0.01). In the presence of global ischemia, both primary and secondary pedicle IP groups had significantly smaller percentage of necrosis than controls (P < 0.05) and there was no significant difference between primary and secondary IP groups (P > 0.05). Thus, IP performed on different pedicles may ameliorate flap survival in a comparable fashion, depending on the duration of global ischemia. Secondary pedicle IP was as effective as primary pedicle IP and may be feasible in free flap transfers. © 2013 Wiley Periodicals, Inc. Microsurgery 34:129–135, 2014. “
“Injury to peripheral nerves always results in progressive skeletal muscle atrophy and poor functional Daporinad in vitro recovery. Previous studies have demonstrated that transplanting neural stem cells (NSCs) into peripheral Cabozantinib purchase nerve can differentiate into neurons and delay muscle atrophy. However, the mechanism was not very clear.

In this study, we transplanted the fetal NSCs to the injured nerve and examined new formed neuromuscular junctions (NMJs) in the denervated muscle and arrest of muscle atrophy. In our study, two pregnant Fischer rats were used to harvest fetal NSCs, 70 rats were randomly divided into NSC-transplanted and control groups, five rats without surgery were used as the normal control. A volume of 5 μl culture media with or without fetal NSCs (5 × 106) were transplanted into distal tibial nerve stump after the nerve was transected in two groups, respectively. Three, five, and seven months after denervation, the dry weight

of gastrocnemius muscle was found significant heavier, and the fiber area was more retained in NSC-transplanted group comparing to the control group (P < 0.05). Neurons were found in the distal tibial nerves even 7 months after fetal NSCs transplantation. Newly formed NMJs were detected by immunohistochemistry. In addition, the results of electrophysiological see more analysis and retrograde tracing manifested that the neural pathway between muscle and differentiated neurons was integrity. In conclusions, our study demonstrated that fetal NSCs transplanted into peripheral nerves could differentiate into neurons and form functional NMJs with denervated muscle, which may be beneficial for the treatment of muscle atrophy after peripheral nerve injury. © 2009 Wiley-Liss, Inc. Microsurgery, 2010. “
“Venous thrombosis is the main cause of radial forearm flap failure, especially when recipient vessels are compromised by prior radiation therapy or neck dissection. In such conditions, semi-free radial forearm flap (SF-RFF) can be performed to reduce this risk. We reviewed all SF-RFF procedures performed in our institution for head and neck reconstruction.

Lectins from Maackia amurensis (MAA, Neu5Acα2,3), Macrobrachium

Lectins from Maackia amurensis (MAA, Neu5Acα2,3), Macrobrachium

rosenbergii (MrL, Neu5,9Ac2-specific) and Arachis hypogaea (PNA, Gal-specific) showed low staining of prion deposits. BMN 673 in vitro Immunohistochemistry colocalization with prion antibody indicated that all lectins stained prion protein deposits. These results show that specific modifications in the glycosylation pattern are closely related to the hallmark lesions and might be an early event in neuronal degeneration in GSS disease. “
“Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease and is the second most common form of young onset dementia after Alzheimer’s disease (AD). An autosomal dominant pattern of inheritance is present in around 25–50% of FTLD cases indicating a strong genetic component. Major pathogenic mutations of FTLD have been demonstrated independently in the progranulin (GRN) gene and the C9orf72 hexanucleotide expansion selleck screening library repeat. In this study we present a family that have been identified as carrying both a GRN Cys31fs mutation and the C9orf72 hexanucleotide expansion repeat. In the present study we describe the clinical and genetic details of family

members and pathological features of two family members that have come to post-mortem. The mean age at disease onset was 57 years (48–61 years) and mean duration 4 years (2–7 years). The most common presenting syndrome was behavioural variant frontotemporal dementia. Brain imaging from available cases showed a symmetrical pattern of atrophy particularly affecting the frontal and temporal lobes. Pathologically two cases were classified as FTLD-TDP type A with TDP-43 positive inclusions, with additional p62-positive ‘star-like’ inclusions found in the hippocampal formation and cerebellum. The type and distribution

of the pathological lesions in these two cases were in keeping with FTLD cases carrying only the C9orf72 hexanucleotide repeat. However the driving force of the pathological process may be either pathogenic mutation or a AMP deaminase combination of both converging on a singular mechanism. “
“F. R. Pereira Lopes, B. C. G. Lisboa, F. Frattini, F. M. Almeida, M. A. Tomaz, P. K. Matsumoto, F. Langone, S. Lora, P. A. Melo, R. Borojevic, S. W. Han and A. M. B. Martinez (2011) Neuropathology and Applied Neurobiology37, 600–612 Enhancement of sciatic nerve regeneration after vascular endothelial growth factor (VEGF) gene therapy Aims: Recent studies have emphasized the beneficial effects of the vascular endothelial growth factor (VEGF) on neurone survival and Schwann cell proliferation.

In situ, IL-33 was highly expressed in the inner nuclear cells of

In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT

mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ+ and IL-17+ CD4+ T cells and reduced Selleckchem Torin 1 IFN-γ and IL-17 production but with increased frequency of IL-5+ and IL-4+ CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis. “
“Interleukin-7 (IL-7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α-chain of the IL-7R is polymorphic with the existence of SNPs that give rise to non-synonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment-related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation

(HCT). Some studies have confirmed an association between check details rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic significance of IL-7Rα SNP genotypes in 590-recipient/donor pairs that received HLA-matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The Tallele of rs6897932 was suggestive of an association with increased frequency

of relapse by univariate analysis (P = 0.017) and multivariate analysis (P = 0.015). In conclusion, this study provides further evidence of a role of the IL-7 pathway and IL-7Rα SNPs in HCT. Interleukin-7 Lumacaftor price (IL-7) is essential for T cell development in the thymus [1] and maintenance of peripheral T cells [2]. IL-7 receptor (IL-7R) consists of the common gamma-chain (CD132) as well as an α-chain (CD127). The α-chain of the IL-7R is polymorphic with the existence of four non-synonymous single nucleotide polymorphisms (SNPs) in the exons; rs1494558 (+510C/T in exon 2), rs1494555 (+1237A/G in exon 4), rs6897932 (+2087T/C in exon 6) and rs3194051 (+3101A/G in exon 8) that all give rise to amino acid substitutions [3, 4]. The α-chain is also used by the receptor of thymic stromal lymphopoietin (TSLP), a cytokine with complex effects on cytokine profiles, including stimulation of TNF production by dendritic cells (DC) and the induction of Th2 cytokines [3, 5, 6].

Although numerous studies have investigated the outcome of exogen

Although numerous studies have investigated the outcome of exogenous or endogenous IL-10 on a variety of infectious and inflammatory animal models, surprisingly few studies have directly addressed if and how IL-10 influences neutrophil responsiveness in vivo or ex vivo. Most in vivo studies, in fact, have overlooked the effects Alvelestat in vitro of IL-10 in different models of inflammation-driven pathologies, including adjuvant- or crystal-induced arthritis 63, 64, zymosan-induced peritoneal inflammation

65, LPS-induced or IgG immune complex-induced acute lung injury 66–68, bacterial or fungal infections 69–71, myocardial- 72, hepatic- 73 or visceral- 74, 75 dependent ischemia-reperfusion injuries, BSA-induced delayed type of hypersensitivity 76, OVA-induced model of asthma 77 and hemorrhagic shock 78. Independent of the type or cause of injury, in all of these studies exogenous IL-10 (or IL-10 gene transfer) effectively reduced the severity of local or systemic inflammation, mainly by blocking cell trafficking, in particular the early influx of neutrophils to the injury site. The reduced accumulation of neutrophils in inflamed organs was ascribed to an IL-10-mediated inhibition of macrophage- or tissue-derived neutrophil chemoattractants 63–68 or, in a single instance, to an IL-10-mediated

increase in neutrophil apoptosis via unidentified mechanisms 79. Conversely, the exacerbated inflammatory reactions occurring in IL-10−/− mice following acute Osimertinib concentration lung inflammation triggered by LPS 80, zymosan-induced

peritonitis 81 or liver injury 82, correlated with increased production of neutrophil chemoattractants and with augmented neutrophil infiltration at inflammatory sites. Additional evidence that IL-10 keeps inflammation under control in vivo by selectively inhibiting the recruitment of neutrophils derives from neutrophil depletion experiments performed in IL-10−/− mice; the combination of a lack of IL-10 and neutrophils decreased the severity of gastritis in Helicobacter felis-infected mice 83. Similarly, mice carrying neutrophil- and macrophage-specific conditional IL-10R1 gene targeting displayed increased sensitivity to LPS in an IL-10-dependent LPS model of endotoxemia 84; a result resembling that described in IL-10−/− mice 80–82 and, additionally, providing supporting for the crucial role of neutrophils (and macrophages) as direct IL-10 cellular targets in vivo. Interestingly, in a recent article, neutrophils were shown to play an important regulatory role during various murine microbial infections in vivo by secreting IL-10 85. In the same study, the authors mention (data not shown) that monocytes, but not neutrophils, from IL-10−/− mice showed a tenfold increase in the production of pro-inflammatory cytokines in response to BCG, indicating that (at least in mice) an autocrine IL-10 regulatory loop controls the monocyte response but does not inhibit pro-inflammatory cytokine production by neutrophils 85.