Immunological Stress Research Articles

More than complementing Tolls: complement-Toll-like receptor synergy and crosstalk in innate immunity and inflammation.

Complement and Toll-like receptors (TLRs) play key roles in the host immune response and are swiftly activated by infection or other types of immunological stress. This review focuses on the capacity of complement and TLRs to engage in signaling crosstalk, ostensibly to coordinate immune and inflammatory responses through synergistic or antagonistic (regulatory) interactions. However, overactivation or dysregulation of either system may lead-often synergistically-to exaggerated inflammation and host tissue injury. Intriguingly, moreover, certain pathogens can manipulate complement-TLR crosstalk pathways in ways that undermine host immunity and favor their persistence. In the setting of polymicrobial inflammatory disease, subversion of complement-TLR crosstalk by keystone pathogens can promote dysbiosis. Knowledge of the molecular mechanisms underlying complement-TLR crosstalk pathways can, therefore, be used productively for tailored therapeutic approaches, such as, to enhance host immunity, mitigate destructive inflammation, or counteract microbial subversion of the host response.

Moderate alcohol consumption after a mental stressor attenuates the endocrine stress response.

Alcohol is often consumed to reduce tension and improve mood when exposed to stressful situations. Previous studies showed that moderate alcohol consumption may reduce stress when alcohol is consumed prior to a stressor, but data on the effect of alcohol consumption after a mental stressor is limited. Therefore, our objective was to study whether moderate alcohol consumption immediately after a mental stressor attenuates the stress response. Twenty-four healthy men (age 21-40y, BMI 18-27kg/m2) participated in a placebo-controlled trial. They randomly consumed 2 cans (660mL, ∼26g alcohol) of beer or alcohol-free beer immediately after a mental stressor (Stroop task and Trier Social Stress Test). Physiological and immunological stress response was measured by monitoring heart rate and repeated measures of the hypothalamic-pituitary-adrenal axis (HPA-axis), white blood cells and a set of cytokines. After a mental stressor, cortisol and adrenocorticotropic hormone (ACTH) concentrations were 100% and 176% more reduced at 60min (P=0.012 and P=0.001, respectively) and 92% and 60% more reduced at 90min (P<0.001 and P=0.056, respectively) after beer consumption as compared to alcohol-free beer consumption. Heart rate and dehydroepiandrosterone (DHEA) were not influenced by alcohol consumption. Plasma IL-8 concentrations remained lower during the stress recovery period after beer consumption than after alcohol-free beer consumption (P<0.001). In conclusion, consumption of a moderate dose of alcohol after a mental stressor may facilitate recovery of the endocrine stress response as reflected by decreasing plasma ACTH and cortisol.

Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged Swine.

Salmonella colonization of food animals is a concern for animal health and public health as a food safety risk. Various obstacles impede the effort to reduce asymptomatic Salmonella carriage in food animals, including the existence of numerous serovars and the ubiquitous nature of Salmonella. To develop an intervention strategy that is non-specific yet effective against diverse Salmonella serovars, we explored the prophylactic use of a cytokine to decrease Salmonella in swine by boosting the host’s innate immune system. Granulocyte-colony stimulating factor (G-CSF) is the major cytokine regulating the production, differentiation, function, and survival of neutrophils. Neutrophils play a critical role in the response to Salmonella; therefore, we evaluated the vectored-delivery of porcine G-CSF as a prophylactic to reduce Salmonella in pigs. Crossbred pigs, 5 weeks of age, were intramuscularly injected with a replication-defective human adenovirus (Ad5) engineered to express porcine G-CSF (Ad5-G-CSF, n = 9). Control pigs received the same Ad5 vector lacking the gene encoding G-CSF (Ad5-empty, n = 7). Four days later, all pigs (n = 16) were intranasally inoculated with 1 × 107 colony forming unit (CFU) of Salmonella enterica serovar Typhimurium UK1. At 2 and 3 days post-challenge with Salmonella, Ad5-G-CSF-treated pigs shed significantly less Salmonella (~103 CFU/g) in their feces than Ad5-empty-treated pigs (~104–105 CFU/g; P < 0.05). A significant 4-log reduction in tonsil colonization was also observed in the Ad5-G-CSF-treated pigs at 7 days post-challenge (P < 0.05). In the gastrointestinal tract, the Peyer’s patch region of the ileum exhibited a significant 0.5-log reduction in colonization in the Ad5-G-CSF-treated pigs (P < 0.05). The microbiota of all challenged pigs was assessed by sequencing and analyzing the V1–V3 region of the 16S rRNA gene from fecal DNA samples. The microbial community structure of Salmonella-challenged pigs was less disturbed post-challenge in the Ad5-G-CSF-treated pigs than the Ad5-empty-treated pigs. This suggests that Ad5-G-CSF administration mitigated changes in the microbial community structure caused by Salmonella challenge. Collectively, these data suggest that delivery of a targeted immunostimulant to enhance neutropoiesis may be a strategy to reduce Salmonella colonization, potentially during periods of immunological stress.

Fermentation products of &lt;i&gt;Cordyceps militaris&lt;/i&gt; enhance performance and modulate immune response of weaned piglets

The aim of this study was to investigate the effect of supplementation of Cordyceps militaris fermentation products (CMF) on growth performance and immunocompetence of piglets. The study involved three groups of animals, which were supplemented with CMF (500, 1000 and 1500 μg/kg feed), and a control group. CMF supplementation significantly increased growth performance in weaned piglets. Bodyweight gain, average daily gain and feed intake in animals supplemented with 1000 μg CMF/kg feed were significantly higher in comparison with the control group. In addition, CMF supplementation only significantly increased the synthesis of Th1 cytokines, as indicated by the levels of IL-2 and IFN-γ. The piglets fed with the CMF supplement displayed an increased cellular immune response. Indeed, alveolar macrophages isolated from piglets supplemented with 1000 and 1500 μg CMF/kg feed had significantly higher chemotactic and phagocytic indices than those isolated from piglets that received the control feed or feed supplemented with 500 μg CMF/kg. In relation to the absence of effect on Th2 cytokines, the CMF supplement had no effect on hog cholera antibody titre. In summary, feed supplementation with CMF improves growth performance and enhances cell-mediated immunity. CMF supplementation may thus be useful at weaning to counteract physiological and immunological stress during this period. Keywords: Cellular immunity, growth performance, humoral immunity, Th1/Th2 cytokines

Protective effects of the prebiotic on the immunological indicators of rainbow trout (Oncorhynchus mykiss) infected with Aeromonas hydrophila.

The aim of this study was to investigate the protective effects of dietary administration of commercial prebiotic, Immunogen, on immunological indicators, enzymatic responses and stress tolerance in juvenile (81.65±1.49) rainbow trout (Oncorhynchus mykiss) following Aeromonas hydrophila infection. The first group of fish was fed with the diet containing 2gkg(-1) Immunogen whilst the control group received the diet free of Immunogen. There were three replicates per group. After 6 weeks feeding, the control group were divided into two treatments injected with saline buffer (control), and 1.5×10(8)CFU A.hydrophila respectively. The fish fed with the Immunogen supplemented diet were also injected with 1.5×10(8)CFU A. hydrophila. Our results revealed that dietary Immunogen increased the level of white blood cell (WBC) and percentage of lymphocyte (P<0.05), however, the level of red blood cell (RBC), Hematocrit (Hct), hemoglobin (Hb) and percent of monocyte decreased in Untreated-Challenged group but unaffected in the group fed with Immunogen (P<0.05). The level of lysozyme, alternative complement, antiprotease activity, total protein, albumin and globulin decreased in Untreated- Challenged group compared to control group. However, there was an increase in the level of lysozyme, alternative complement, antiprotease activity, bactericidal activity, in the Treated- Challenged group compared to other groups (P<0.05). Serum alkali phosphatase (ALT) and aspartate aminotransferase, significantly increased fallowing challenge with A. hydrophila but in the Treated-Challenged group, there was no significant difference compared to the control group (P<0.05). Lactate dehydrogenase (LDH) level was not different between groups (P>0.05). Serum cortisol and glucose levels were higher in the challenge group, but these levels were lower in fish under challenge that were fed Immunogen-supplemented diet in contrast to the group fed control diet. The stress responses affected by A. hydrophila challenge (P<0.05). Serum sodium, potassium and calcium concentration decreased by A. hydrophila exposure (P<0.05), and Immunogen showed protection effect against this change.

Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia.

BackgroundIn schizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger the changes that lead to impaired neuronal functions. Cytokines being the key regulators of immune/inflammatory reactions are also known to influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. Therefore, functional polymorphisms in cytokine genes may result in imbalances in the pro- and anti-inflammatory cytokine production.MethodsWe screened polymorphisms in pro- and anti-inflammatory cytokine genes using a case-control association study in a South Indian population. The role of allele, genotype, haplotype, and diplotypes of these cytokine genes and their epistatic interactions were assessed in contributing to the risk of developing schizophrenia. Meta-analysis for the reported associations was also monitored for global significance.ResultsThe pro-inflammatory cytokine gene polymorphisms in IL1Ars1800587, IL6rs1800796, TNFArs361525, and IFNGrs2069718 were associated with schizophrenia. The study also provides significant evidence for strong epistatic interactions among pro-inflammatory cytokine genes IL6 and IFNG in the development of schizophrenia. In silico analysis suggested that associated risk variants were indicative of altered transcriptional activity with higher production of IL1α, IL-6, TNF-α, and IFN-ɤ cytokines. Meta-analysis indicated heterogeneity among study population while IL1Ars1800587 was found to be globally significant.ConclusionsIt is important to identify the nature of inflammatory response that can be amplified by the environment, to influence either Th1 response or Th2 response. The associated functional variants in the study are involved with increased expression resulting in higher production of the pro-inflammatory cytokines IL-1α, IL-6, TNF-α, and IFN-γ. The interaction of immunological stressors with these high producer alleles of pro-inflammatory cytokines may suggest that even a lower threshold may be sufficient to induce a resultant chronic effect on the psycho-social and environmental stressors that may result in the development and pathogenesis of schizophrenia. Understanding environmental factors that influence the expression of these pro-inflammatory cytokine genes or their interaction can possibly help in dissecting the phenotypic variation and therapeutic response to antipsychotics in schizophrenia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0569-8) contains supplementary material, which is available to authorized users.

Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice.

The capacity of pancreatic β cells to maintain glucose homeostasis during chronic physiologic and immunologic stress is important for cellular and metabolic homeostasis. Insulin receptor substrate 2 (IRS2) is a regulated adapter protein that links the insulin and IGF1 receptors to downstream signaling cascades. Since strategies to maintain or increase IRS2 expression can promote β cell growth, function, and survival, we conducted a screen to find small molecules that can increase IRS2 mRNA in isolated human pancreatic islets. We identified 77 compounds, including 15 that contained a tricyclic core. To establish the efficacy of our approach, one of the tricyclic compounds, trimeprazine tartrate, was investigated in isolated human islets and in mouse models. Trimeprazine is a first-generation antihistamine that acts as a partial agonist against the histamine H1 receptor (H1R) and other GPCRs, some of which are expressed on human islets. Trimeprazine promoted CREB phosphorylation and increased the concentration of IRS2 in islets. IRS2 was required for trimeprazine to increase nuclear Pdx1, islet mass, β cell replication and function, and glucose tolerance in mice. Moreover, trimeprazine synergized with anti-CD3 Abs to reduce the progression of diabetes in NOD mice. Finally, it increased the function of human islet transplants in streptozotocin-induced (STZ-induced) diabetic mice. Thus, trimeprazine, its analogs, or possibly other compounds that increase IRS2 in islets and β cells without adverse systemic effects might provide mechanism-based strategies to prevent the progression of diabetes.

The Most Common Herbs to Cure the Most Common Oral Disease: Stomatitis Recurrent Aphthous Ulcer (RAU).

Context:Recurrent aphthous ulcer (RAU) is an oral disease and the most common oral lesion, with 2% to 66% of the world’s population infected annually. Its prevalence is about 25% in Tehran and 27.6% in Mashhad. The etiology of RAU is multifactorial. Aphthous risk factors include: immunological factors, psychological factors, stress, trauma, sensitivity, family history, blood disorders, malnutrition, and use of certain medications, It should be noted that the best treatment for RAU is the topical application of drugs. The use of topical treatments is recommended not only because the drug can directly impact the source of the disease, but also systemic side effects of the drug are reduced. Treatment of RAU has been considered in Iranian traditional medicine (ITM), and is covered in therapeutic books. The use of herbs in RAU has a centuries-old history; accordingly, extensive research should be conducted for this treatment of the disease.Evidence Acquisition:Iranian medical sources were reviewed and effective plants used in the traditional treatment of RAU were found and compared with new findings. Finally, we have created a table listing the plants that are part of the therapeutic protocol for RAU.Results:Based on this article we can explain some of traditional pharmacological effects of plants and how these plants can be a source for a cure.Conclusions:The plants listed can be used as a prediction of RAU management. Of course, there are is no evidence for curing RAU by some of these plants in allopathic medicine, and the further investigations in this area could lead to the discovery of a new drug

Analysis of Ionomic Profiles of Canine Hairs Exposed to Lipopolysaccharide (LPS)-Induced Stress.

The purpose of this study was to provide a new insight on the response of canines to stress exposure; the ionomic profiles of canine hair (2.8 ± 0.3years, 15.17 ± 2.1kg) (n = 10) was determined before and after lipopolysaccharide (LPS) injections. LPS was intramuscularly injected to induce inflammatory stress responses which were confirmed by observing increases in the level of serum cortisol, aldosterone, and inflammatory cytokines such as IL-6, IL-1β, and TNF-α. The hair contents of 17 elements were obtained by applying analytical procedures using the inductively coupled plasma mass spectrometry (ICP-MS). The following elements: sodium(Na) and potassium(K) among macro-elements, iron(Fe) and manganese(Mn) among micro-elements, and aluminum(Al), nickel(Ni), and lead(Pb) for toxic elements, showed significant increased levels with the immunological stress. The degree of increase in toxic elements was remarkable with the stress exposure. A forty-five-fold increase seen in Al accumulation with the stress exposure was noteworthy. Although mercury(Hg) and cadmium(Cd) showed decreased levels with the stress exposure, the degree was negligible compared to the level of increase. Correlation pattern between the elements was changed with the immunological stress. Toxic elements became more correlated with macro- or micro-elements than with toxic elements themselves after the stress exposure. Principal component analysis (PCA) showed that LPS challenge shifted the overall hair mineral profiles to a consistent direction changing Al and K up, even in animals with different hair mineral profiles before LPS treatment. In conclusion, the multivariate data processing and study of element distribution patterns provided new information about the ionomic response of the canine hairs to immunological stress, i.e., the ionomic profiles of canine hairs is strongly affected by the stress induced by LPS injections.

Influence of environmental stress on immunity of swine

This paper deals with pigs kept in environments, where they are exposed to a high number of pathogenic microbes and have reduced feed intake and growth, even when no obvious acute illness exists. According to the presented article this chronic drain on production is called immunologic stress. Sentinel immune cells (e.g. macrophages) supervise the diverse microbial environment by detecting pathogen – associated molecular patterns (PAMPs), which are molecules associated with groups of pathogens. The immune sentinels detect PAMPs mainly with Toll – like receptors (TLRs). Stimulation of macrophages through their TLRs leads to the synthesis and secretion of pro-inflammatory cytokines and prostaglandins, initiating the inflammatory response that recruits both immune molecules and circulating immune cells. Pro-inflammatory cytokines enable the immune system to communicate with other physiological systems. They rearrange the animal’s metabolic priorities, resulting in re-partitioning of nutrients away from productive processes towards responses that support the immune system. Thus, the immune system, through detection of PAMPs and production of pro-inflammatory cytokines, is the critical chain link connecting the pathogenic environment to productivity. The evaluation indicates, that at maintenance a healthy animal uses about 0,5-2% of the body’s lysine for leucocytes, antibodies and acute phase proteins. In the situation of contamination by pathogens of the environment the immune response is estimated to account for about 9% of the body’s lysine. Providing additional lysine in the diet does not improve the reduced growth of the pig, caused by immunologic stress as the result of contamination of the pig environment by pathogenic or facultatively pathogenic microorganisms. Thus, minimizing exposure to pathogenic microorganisms and providing sound environmental management practices is a high priority.

Effects of Official Basketball Competition on the Levels of Cortisol and Salivary Immunoglobulin (A) among female children

Aim: The purpose of the study was to investigate the effect of Official basketball competition on the levels of Cortisol and Immunoglobulin A among pre pubertal girls of 10-11 years old. Method: The statistical population of the study consisted of 12 female basketball players with an average age of (10.58 ± 0.15 years).Collection of the salivary specimen was conducted in accordance with the standard procedures, before and immediately five minutes after the competition. Cortisol concentration and Salivary IgA level were measured, using ELISA quantitative method. Statistical analysis was conducted using the dependent t-Test. Results: the results revealed that an official basketball competition increases cortisol and salivary IgA concentrations, significantly (p ≤ 0.00).Regarding the results of the analysis, one may conclude that sport competition is likely to affect physiological responses of the children and juvenile’s immune systems. Conclusion: It worth to note that despite widespread participation of children and juveniles in competitions and sport events, little researches have been conducted on their immunological factors and stress hormones in response to stressful conditions dominated over the competitions and sport events. Even insufficient information and data achieved through investigations are necessary and useful in evaluation of this age group, concerning their hormone responses to the competitions and sport events.

Protective role of biogenic selenium nanoparticles in immunological and oxidative stress generated by enrofloxacin in broiler chicken.

Presently most bacteria are becoming antibiotic resistant. Due to this there is a deficiency of potent antibiotics, therefore we have to preserve and improve the efficiency of existing antibiotics by mitigating the side effects. Enrofloxacin (EFX) is an important antimicrobial used in veterinary practice but it is known to exert immune suppression antioxidant stress. In the present study, we report on: (a) the biosynthesis of selenium nanoparticles (Se NPs), and (b) their protective effect in reducing adverse effects of EFX on broiler chicken. A potent bacterial strain, isolated from farm soil, has been identified as Pantoea agglomerans (GenBank: KU500622). It tolerates a high concentration of selenium dioxide (9 mM) and produces Se NPs under aerobic conditions. The obtained Se NPs are amorphous in structure and spherical in shape with sizes of less than 100 nm. The activity of cellular, humoral immune response and enzymatic and non-enzymatic antioxidants, has significantly been decreased as a result of EFX treatment. We investigated that Se NP supplementation greatly restores these values towards the control, and to even higher than those of the control. Adverse effects of EFX are prevented by simultaneous exposure to Se NPs (0.6 mg per kg of feed) in the diet of poultry chicken.

Sexual dimorphism in the mast cell transcriptome and the pathophysiological responses to immunological and psychological stress

Sexual dimorphism in the mast cell transcriptome and the pathophysiological responses to immunological and psychological stress

CONSUMPTION OF CHERRIES AS A STRATEGY TO ATTENUATE EXERCISE-INDUCED MUSCLE DAMAGE AND INFLAMMATION IN HUMANS.

exercise-induced muscle damage (EIMD) is a multifactorial phenomenon that induces muscle function loss because of mechanical and immune stressor stimuli. This immunological stress is mostly caused by inflammation and increased oxidative status. Cherries are fruits that contain a phenolic compound known as anthocyanin, which serves as a pigment in natura. However, research suggests this pigment might provide a potent antioxidant and anti-inflammatory strategy when consumed by humans. the aim of this study was to critically review the literature on cherry consumption focusing on identifying protective strategies against EIMD conferred by it. a research was performed in PubMed database. This review presents the results about cherry consumption and EIMD. the articles identified in this review support the notion that tart cherry consumption attenuates EIMD symptoms after intense exercise bouts. This attenuation seems to be related to the antioxidant and anti-inflammatory properties of anthocyanins and other phenolic compounds present in tart cherries. daily consumption of tart cherries may attenuate inflammatory and oxidative responses to EIMD, leading to faster recovery after exercise bouts.

Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial – the PRODIGE 22 - ECKINOXE trial

BackgroundIn patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30 % of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery.Methods/DesignPRODIGE 22 - ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and completeness of the surgery, initial radiological staging and radiological response to neoadjuvant chemotherapy, and the correlation between histopathological and radiological response. Taking into account a 50 % prevalence of CC without RAS mutation, accrual of 165 patients is needed for this Phase II trial.Trial RegistrationNCT01675999 (ClinicalTrials.gov)

Immunological dependence of plant-dwelling animals on the medicinal properties of their plant substrates: a preliminary test of a novel evolutionary hypothesis

We present preliminary evidence for a novel evolutionary hypothesis, i.e., that animals living on plants high in antimicrobial secondary metabolites could, via drift or selection, evolve weakened immune defenses and an immunological dependence on the antimicrobial properties of their plant substrate and/or the volatile mix in the air surrounding their plant. Animals experience immunological stress during developmental transitions, so we evaluated our hypothesis by testing for an effect of plant substrate on hatching success in the jumping spider Lyssomanes viridis, a species that constructs its egg sacs on Liquidambar styraciflua leaves. Compared with other sympatric species, L. styraciflua is known to be high in potent volatile broad-spectrum antimicrobial compounds, most notably, the monoterpene terpinen-4-ol, a well-studied antimicrobial agent known from tea tree oil. We found that L. viridis experience higher hatching success on L. styraciflua than on other sympatric species or plastic substrate controls and that L. viridis has a chemically mediated preference for this plant. In contrast to other spiders’ compact, densely woven egg sacs, L. viridis’ egg sacs are sparsely woven and the eggs widely spaced, maximizing the eggs’ surface area exposed to volatiles coming off the leaf. Similar architectures exist in distantly related taxa, suggesting convergent evolution. Our theoretical framework and preliminary results open up an unexplored frontier—the possibility that any number of plant-dwelling species may depend upon on the antimicrobial properties of the plant tissues they inhabit.

Systemic immunity shapes the oral microbiome and susceptibility to bisphosphonate-associated osteonecrosis of the jaw.

BackgroundOsteonecrosis of the jaw (ONJ) is a rare but serious adverse drug effect linked to long-term and/or high-dose exposure to nitrogen-bisphosphonates (N-BP), the standard of care for the treatment of bone fragility disorders. The mechanism leading to bisphosphonate-associated ONJ (BAONJ) is unclear and optimal treatment strategies are lacking. Recent evidence suggests that BAONJ may be linked to drug-induced immune dysfunction, possibly associated with increased susceptibility to infections in the oral cavity. The objective of this investigation was to comprehensively assess the relationship linking immune function, N-BP exposure, the oral microbiome and ONJ susceptibility.MethodsLeukocyte gene expression of factors important for immunity, wound healing and barrier function were assessed by real-time quantitative PCR and the oral microbiome was characterized by 454 pyrosequencing of the 16S rRNA gene in 93 subjects stratified by N-BP exposure and a history of ONJ.ResultsThere were marked differences in the systemic expression of genes regulating immune and barrier functions including RANK (p = 0.007), aryl hydrocarbon receptor (AHR, p < 0.001), and FGF9 (p < 0.001), which were collectively up-regulated in individuals exposed to N-BP without ONJ relative to treatment controls. In contrast, the expression levels of these same genes were significantly down-regulated in those who had experienced BAONJ. Surprisingly, the oral microbiome composition was not directly linked to either BAONJ or N-BP exposure, rather the systemic leukocyte expression levels of RANK, TNFA and AHR each explained 9% (p = 0.04), 12% (p = 0.01), and 7% (p = 0.03) of the oral bacterial beta diversity.ConclusionsThe oral microbiome is unlikely causative of ONJ, rather individuals with BAONJ lacked immune resiliency which impaired their capacity to respond adequately to the immunological stress of N-BP treatment. This may be the common factor linking N-BP and anti-RANK agents to ONJ in at-risk individuals. Preventive and/or therapeutic strategies should target the wound healing deficits present in those with ONJ.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0568-z) contains supplementary material, which is available to authorized users.

Bacillus amyloliquefaciens supplementation alleviates immunological stress in lipopolysaccharide-challenged broilers at early age

This study was conducted to investigate the effect of Bacillus amyloliquefaciens (BA) on the immune function of broilers challenged with lipopolysaccharide (LPS). 192 one-day-old male Arbor Acre broiler chickens were randomly distributed into four treatments: 1) broilers fed a basal diet; 2) broilers fed a basal diet supplemented with BA; 3) LPS-challenged broilers fed a basal diet; and 4) LPS-challenged broilers fed a basal diet supplemented with BA. Each treatment consisted of six replicates with eight broilers per replicate. Broilers were intraperitoneally injected with either 500 μg LPS per kg body weight or sterile saline at 16, 18 and 20 d of age. LPS decreased the average daily gain (ADG, P = 0.001) and average daily feed intake (P = 0.001). The decreased ADG (P = 0.009) and increased feed conversion ratio (P = 0.047) in LPS-challenged broilers were alleviated by BA. LPS increased the relative spleen weight (P = 0.001). Relative spleen (P = 0.014) and bursa (P = 0.024) weights in the LPS-challenged broilers were reduced by BA. LPS increased white blood cell (WBC) numbers (P = 0.001). However, the WBC numbers (P = 0.042) and the ratio of lymphocytes to WBC (P = 0.020) in LPS-challenged broilers were decreased with BA treatment. LPS decreased plasma lysozyme activity (P = 0.001), but increased concentrations of plasma corticosterone (P = 0.012) and IL-2 (P = 0.020). In contrast, BA increased lysozyme activity in plasma (P = 0.040). LPS increased mRNA abundances of splenic toll-like receptor 4 (P = 0.046), interferon γ (P = 0.008), IL- 1β (P = 0.045) and IL-6, (P = 0.006). IL-2 (P = 0.014) and IL-6 (P = 0.074) mRNA abundances in LPS-challenged broilers were reduced by BA, although BA had an opposite effect for IL-10 mRNA expression in those broilers (P = 0.004). In conclusion, BA supplementation could partially alleviate the compromised growth performance and immune status of broilers under immune stress induced by LPS challenge at early age.

Improving Our Children's Health Is an Investment Priority.

Improving Our Children's Health Is an Investment Priority.

Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are chronic disorders of modern society, requiring management strategies aimed at prolonging an active life and establishing the exact etiology and pathogenesis. These idiopathic diseases have environmental, genetic, immunologic, inflammatory, and oxidative stress components. On the one hand, recent advances have shown that abnormal immune reactions against the microorganisms of the intestinal flora are responsible for the inflammation in genetically susceptible individuals. On the other hand, in addition to T helper cell-type (Th) 1 and Th2 immune responses, other subsets of T cells, namely regulatory T cells and Th17 maintained by IL-23 are likely to develop IBD. IL-23 acts on innate immune system members and also facilitates the expansion and maintenance of Th17 cells. The IL-17/IL-23 axis is relevant in IBD pathogenesis both in human and experimental studies. Novel biomarkers of IBD could be calprotectin, microRNAs, and serum proinflammatory cytokines. An efficient strategy for IBD therapy is represented by the combination of IL-17A and IL-17F in acute IL-17A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17F knockout, DSS-induced colitis have been observed. Studying the correlation between innate and adaptive immune systems, we hope to obtain a focused review in order to facilitate future approaches aimed at elucidating the immunological mechanisms that control gut inflammation.