Acute Phase Immune Response Research Articles

Bacterial-induced maternal interleukin-17A pathway promotes autistic-like behaviors in mouse offspring.

Maternal immune activation (MIA) by an infection is considered to be an important environmental factor of fetal brain development. Recent animal model on MIA induced by polyinosinic:polycytidylic acid, a mimic of viral infection, demonstrates that maternal IL-17A signaling is required for the development of autism spectrum disorder (ASD)-like behaviors of offspring. However, there is little information on bacterial infection. In this study, we aim to elucidate the influence of MIA induced by lipopolysaccharide (LPS) to mimic a bacterial infection on fetal brain development. We demonstrated that LPS-induced MIA promoted ASD-like behaviors in mouse offspring. We further found that LPS exposure induced acute phase immune response: elevation of serum IL-17A levels in MIA mothers, upregulation of Il17a mRNA expression and increase of IL-17A-producing γδ T cells in the uterus, and upregulation of Il17ra mRNA expression in the fetal brain. Blocking of IL-17A in LPS-induced MIA ameliorated ASD-like behaviors in offspring. Our data suggest that bacterial-induced maternal IL-17A pathway promotes ASD-like behaviors in offspring.

Abstract WP564: Deep Immune Profiling of the Post-Stroke Peripheral Immune Response Reveals Tri-phasic Response and Correlations With Long-Term Cognitive Outcomes

Introduction: Stroke produces profound local and systemic immune responses that engage all major innate and adaptive immune compartments. The aim of this study was to characterize the systemic immune response to stroke and to determine if it contributes to long-term cognitive disability. Methods: We included 24 consecutive subjects with ischemic stroke and excluded patients for autoimmune disorders, use of immunosuppressant drugs, or life expectancy <90 days. Blood samples were collected for up to 9 timepoints after stroke (days 1, 2, 3, 5, 7, 14, 30, 90, and 365). Change in cognitive function between days 90 and 365 was assessed using the Montreal Cognitive Assessment (MoCA). Control samples were from a cohort of 24 sex- and age-matched patients prior to hip replacement surgery. We used mass cytometry to acquire 240 immune features from each sample, representing 20 immune cell subtypes, their frequency, cell surface markers, and activation states. Elastic Net (EN) regularized regression modeling was used to characterize phases of the immune response and to correlate stages of the immune response with change in cognitive function. Results: The EN model identified three distinct phases of the systemic immune response to ischemic stroke: The acute phase (day 2) was characterized by increased STAT3 (signal transducer and activator of transcription 3) signaling responses in innate immune cell types. The intermediate phase (day 5) was characterized by increased CREB (cAMP response element-binding protein) signaling responses in adaptive immune cell types. The late phase (day 90) was characterized by persistent elevation of neutrophils and IgM+ B cells. By day 365 there was a return to baseline immune responses, comparable to the controls. A decline in MoCA scores between day 90 and day 365 after stroke correlated with a stronger inflammatory response in the acute phase (r = -0.692, Bonferroni-corrected p = 0.04). Conclusions: The results demonstrate three distinct phases of the peripheral immune response that occur after stroke, spanning from days 2 to day 90. The acute phase immune response predicts post-stroke cognitive decline, suggesting that therapies aimed at optimizing this response could lead to preservation of cognitive functioning post-stroke.

Host preference of a haematophagous avian ectoparasite: a micronutrient supplementation experiment to test an evolutionary trade-off

Immune responses vary greatly depending on physiological and ecological circumstances, but the causes of this variation and its consequences for host–parasite interactions are not clear. One problem is whether resource trade-offs within hosts affect host choice by macroparasites. We aimed experimentally to disentangle the effects of the nutritional and immunological parameters of the host on the choice of host by a blood-feeding ectoparasitic fly, Carnus hemapterus. We used micronutrient supplementation to enhance host immunity and antioxidant capacity and balance the resource allocation of the host from growth to immune function in nestlings of the European roller, Coracias garrulus. Micronutrient-supplemented nestlings showed lower growth rate and body condition than sham-supplemented nestlings. Nestlings receiving micronutrients also had a higher albumin-to-globulin ratio and β- and γ-globulin concentrations, but lower α1- and α2-globulin concentrations, total protein level and cutaneous response to phytohaemagglutinin. Our results revealed that the phytohaemagglutinin response and β- and γ-globulin concentrations reflect body condition, whereas the strength of the acute phase response (α1- and α2-globulin concentrations) reflects the protein status in nestling European rollers. Ectoparasitic C. hemapterus flies generally chose hosts according to their body condition. However, this choice was moderated by host immunity when the host had poor body condition or posed a high risk for parasites in terms of the acute phase immune response.

Density measurement of Demodex canis by qPCR and analysis of serum cytokine levels in dogs with different clinical forms of demodicosis

ObjectivesTo quantify (by qPCR) the density of Demodex canis mites in the skin of dogs with demodicosis and in healthy dogs, as well as measuring the serum concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, and tumour necrosis factor-alfa (TNF-α). MethodsFifty-four dogs were divided into three groups: localized demodicosis (LD, n = 16), generalized demodicosis (GD, n = 22), and control group (CG, n = 16). All dogs were subjected to skin scraping, blood collection, and skin biopsy. DNA extraction was performed and the parasite density was established by qPCR. Serum cytokine concentrations were obtained by flow cytometry. ResultsThe median number of mites in the skin of the GD (6.2 × 104 copies/μL) and LD dogs (1.2 × 104 copies/μL) was statistically higher than that in the CG dogs (8.7 × 102 copies/μL). Whereas there were no significant differences in median IL-1β, IL-8, IL-10, IL-12, and TNF-α levels among the study groups, there was a statistically higher IL-6 concentration in the LD dogs than in the healthy dogs. ConclusionsAccording to our results, qPCR is an effective method for measuring the density of D. canis in the canine integument. In addition, the activation of the acute-phase immune response in localized demodicosis can be induced by IL-6 activity.

Repeated immune challenges affect testosterone but not sperm quality.

Mounting an immunological response is energetically demanding and necessarily redirects allocation of resources toward immune system activation and away from other energetically expensive processes, such as reproduction. Lipopolysaccharide (LPS), a major component of the outer membrane of the cell wall of Gram-negative bacteria Escherichia coli, mimics a bacterial infection without producing the cost of replicating the pathogen and is one of the most commonly used agents to induce an acute phase immune response. Here, we ask if a trade-off can be induced between activation of the acute phase immune response and sperm function, a key indicator of sperm competitive ability. Further, we ask whether repeated exposure to this endotoxin in a social species such as the house sparrow (Passer domesticus), where repeated pathogen exposure may be common, may have a more pronounced effect. To address our questions, we exposed individuals to two rounds of LPS treatment or control, to mimic a repeated pathogen exposure in the wild. We predicted that repeated pathogen exposure would have detrimental effects on sperm quality, and therefore, reproductive success. We compared a measure of sperm quality (straight-line velocity) in captive male house sparrows between LPS-treated and control individuals. We found that although LPS treatment impaired circulating testosterone and induced a hypothermic state when compared with controls, it did not affect sperm quality within days or weeks following a single or repeated LPS exposure.

Peripheral zinc and neopterin concentrations are associated with mood severity in bipolar disorder in a gender-specific manner

Bipolar disorder (BD) is a recurrent, episodic mood disorder for which there are no current diagnostic, prognostic or theranostic biomarkers. Two peripheral markers of the acute phase immune response, zinc and neopterin, are consistently associated with severity of depression in literature. Given gender differences in clinical presentation of BD and in inflammatory processes, we aimed to explore the interaction between gender and immune biomarkers to predict mood severity in BD. Participants with DSM IV BD I and II were recruited through the Pennsylvania Psychiatric Institute during an acute mood episode. Healthy controls (HC) were recruited through advertisements. Participants fasted for at least 6h when blood was drawn for biomarkers. We found that zinc concentrations were significantly lower in the BD group at baseline (p<.05), and there was also a significant interaction between gender and zinc (p<.05), associated with depression severity. Also, we found a significant interaction between gender and neopterin, associated with mania severity (p<.05). We found that mania severity was associated with neopterin in men, while depression severity was positively associated with zinc in women. Our report bears replication in larger samples and highlights the potential for differences in the underlying pathophysiology between men and women with BD.

Whole Blood Cytokine Response to Local Traffic-Related Particulate Matter in Peruvian Children With and Without Asthma.

This study sought to investigate if acute phase immune responses of whole blood from Peruvian children with controlled and uncontrolled asthma differed from children without asthma, following exposure to traffic-related particulate matter (TRPM). TRPM, including particulate matter from diesel combustion, has been shown to stimulate acute airway inflammation in individuals with and without asthma. For this study, a whole blood assay (WBA) was used to test peripheral whole blood samples from 27 children with asthma, and 12 without asthma. Participant blood samples were stimulated, ex vivo, for 24-h with an aqueous extract of TRPM that was collected near study area highways in Lima, Peru. All participant blood samples were tested against the same TRPM extract, in addition to purified bacterial endotoxin and pyrogen-free water, which served as positive and negative WBA controls, respectively. The innate and adaptive cytokine responses were evaluated in cell-free supernatants of the whole blood incubations. Comparatively similar levels were recorded for nine out of the 10 cytokines measured [e.g., – Interleukin (IL)-1β, IL-6, IL-10], regardless of study participant asthma status. However, IL-8 levels in TRPM-stimulated blood from children with uncontrolled asthma were diminished, compared to subjects without asthma (633 pg/ml vs. 1,023 pg/ml, respectively; p < 0.01); IL-8 responses for subjects with controlled asthma were also reduced, but to a lesser degree (799 pg/ml vs. 1,023 pg/ml, respectively; p = 0.10). These relationships were present before, and after, adjusting for age, sex, obesity/overweight status, C-reactive protein levels, and residential proximity to the study area’s major roadway. For tests conducted with endotoxin, there were no discernible differences in cytokine response between groups, for all cytokines measured. The WBA testing conducted for this study highlighted the capacity of the TRPM extract to potently elicit the release of IL-8 from the human whole blood system. Although the small sample size of the study limits the capacity to draw definitive conclusions, the IL-8 responses suggest that that asthma control may be associated with the regulation of a key mediator in neutrophil chemotaxis, at a systemic level, following exposure to PM derived from traffic-related sources.

P.2.d.018 - Clinical correlates of age at onset distribution in bipolar disorder: a comparison between diagnostic subgroups

Bipolar disorder (BD) is a recurrent, episodic mood disorder for which there are no current diagnostic, prognostic or theranostic biomarkers. Two peripheral markers of the acute phase immune response, zinc and neopterin, are consistently associated with severity of depression in literature. Given gender differences in clinical presentation of BD and in inflammatory processes, we aimed to explore the interaction between gender and immune biomarkers to predict mood severity in BD. Participants with DSM IV BD I and II were recruited through the Pennsylvania Psychiatric Institute during an acute mood episode. Healthy controls (HC) were recruited through advertisements. Participants fasted for at least 6 h when blood was drawn for biomarkers. We found that zinc concentrations were significantly lower in the BD group at baseline (p<.05), and there was also a significant interaction between gender and zinc (p<.05), associated with depression severity. Also, we found a significant interaction between gender and neopterin, associated with mania severity (p<.05). We found that mania severity was associated with neopterin in men, while depression severity was positively associated with zinc in women. Our report bears replication in larger samples and highlights the potential for differences in the underlying pathophysiology between men and women with BD.

The growth endocrine axis and inflammatory responses after laparoscopic cholecystectomy.

It is well known that conventional surgery leads to detrimental immune and catabolic responses, thus there is growing interest in the effect of minimally invasive techniques on postoperative endocrine and immune function. The aim of this prospective study was to evaluate the growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/IGF binding protein-3 (IGFBP-3) axis and acute phase (interleukin-6, IL-6, and C-reactive protein, CRP) responses in patients who underwent laparoscopic cholecystectomy. Twenty-nine patients (16 women, 13 men; age: 58+8 years) with a history of uncomplicated symptomatic cholelithiasis participated in the study. Blood samples were collected prior to and at 24 hrs and 48 hrs after laparoscopic cholecystectomy. Serum concentrations of GH, IGF-1, IGFBP-3, and IL-6 were determined by standard sandwich enzyme-linked immunosorbent assay (ELISA), while CRP was measured by nephelometry. ANOVA with repeated measures and Tukey's post-hoc test were used to evaluate changes in serum measurements. The laparoscopic cholecystectomy resulted in a significant postoperative increase in circulating levels of IL-6 (p=0.031), which is the main cytokine responsible for inducing the acute inflammatory response, and of the acute phase protein CRP (p=0.005). A significant increase in GH levels at 24 hrs (p=0.034) and decrease of IGF-1 on both postoperative days were also found (p=0.045, 0.044), while no changes were documented in IGFBP-3 levels. Significant correlations were revealed between postoperative levels of the acute phase proteins and growth axis hormones (p<0.05 - 0.001). Our findings suggest that laparoscopic cholecystectomy induces acute phase endocrine and immune responses. These changes may represent a state of systemic inflammation and GH resistance, compatible with possible cytokine-induced anti-anabolic or catabolic effects even after this minimally invasive cholecystectomy.

Interleukin-10 as an indicator of chronic course of oral candidiasis in diabetics: an in vitro study

The importance of host defense against candidiasis and the role of cell-mediated immunity in host defense have been the subject of many studies. Increased expression of virulence factors in Candida isolates from diabetes mellitus (DM) patients with oropharyngeal candidiasis (OPC) has also been reported. To study the difference in T helper type 2 (Th2) and T helper type 1 (Th1) responses and neutrophil respiratory burst response, as a parameter of acute phase and adaptive immune responses, respectively, by using Candida isolates from lesions of oropharyngeal candidiasis (OPC) in DM patients compared to oral Candida isolates from healthy carriers. Analytical experimental laboratory-based study: (a) yeast identification and speciation was done. (b) Peripheral blood mononuclear cells (PBMCs) and neutrophils, obtained from healthy volunteers, were stimulated with oral Candida isolates of DM patients and healthy carriers (controls). Thereafter, cytokine analysis and neutrophil respiratory burst response analysis were done. IL-10 release was uniformly low at all concentrations of Candida albicans antigen isolated from healthy controls as compared to when C. albicans isolated from DM patients was used as antigenic stimulus. Mean INF-γ concentration was highest when C. albicans, isolated from healthy carriers was used as antigenic stimulus for PBMCs. There was no significant difference in neutrophil respiratory burst response among study and control groups. The observations highlight a significant IL-10 dominance, which may be an indicator of the inclination of host immune system toward a chronic progressive disease condition, indicating the pathogenic potential of select Candida strains.

Identification and structural comparison of deleterious mutations in nsSNPs of IL-6 gene in inflammation: A bio-informatics study

IL 6 is a pro-inflammatory cytokine involved in driving inflammation and the acute phase immune response. Hence, it is important to predict SNPs which could affect IL-6 stability and thus inflammatory conditions. Therefore, this study was undertaken to find the functional nsSNPs in IL 6. Out of total 243 SNPs, 37 were nsSNPs (non-synonymous), 7 occurred in the mRNA 3’UTR, 7 occurred in 5’ UTR region, 193 occurred in intronic regions and rest were other types of SNPs. Among the predicted nsSNPs, rs2069860, rs11544633 were identified as deleterious and damaging by different programs. Additionally, I-Mutant showed a decrease in stability for these nsSNPs upon mutation. Protein structural analysis with these amino acid variants was performed by using I-Mutant and Swiss PDB viewer to check their molecular dynamics and energy minimization calculations. We also identified several IL 6 sites that may undergo post-translational modification, including sites that coincide with the location of high-risk nsSNPs. This study suggested that D162V and P119L variants of IL 6 could directly or indirectly destabilize the amino acid interactions and could be useful for evaluation of genotype association study with inflammatory diseases.

Effects of dietary Capsicum oleoresin on productivity and immune responses in lactating dairy cows

This study investigated the effect of Capsicum oleoresin in granular form (CAP) on nutrient digestibility, immune responses, oxidative stress markers, blood chemistry, rumen fermentation, rumen bacterial populations, and productivity of lactating dairy cows. Eight multiparous Holstein cows, including 3 ruminally cannulated, were used in a replicated 4×4 Latin square design experiment. Experimental periods were 25 d in duration, including a 14-d adaptation and an 11-d data collection and sampling period. Treatments included control (no CAP) and daily supplementation of 250, 500, or 1,000 mg of CAP/cow. Dry matter intake was not affected by CAP (average 27.0±0.64 kg/d), but milk yield tended to quadratically increase with CAP supplementation (50.3 to 51.9±0.86 kg/d). Capsicum oleoresin quadratically increased energy-corrected milk yield, but had no effect on milk fat concentration. Rumen fermentation variables, apparent total-tract digestibility of nutrients, and N excretion in feces and urine were not affected by CAP. Blood serum β-hydroxybutyrate was quadratically increased by CAP, whereas the concentration of nonesterified fatty acids was similar among treatments. Rumen populations of Bacteroidales, Prevotella, and Roseburia decreased and Butyrivibrio increased quadratically with CAP supplementation. T cell phenotypes were not affected by treatment. Mean fluorescence intensity for phagocytic activity of neutrophils tended to be quadratically increased by CAP. Numbers of neutrophils and eosinophils and the ratio of neutrophils to lymphocytes in peripheral blood linearly increased with increasing CAP. Oxidative stress markers were not affected by CAP. Overall, in the conditions of this experiment, CAP did not affect feed intake, rumen fermentation, nutrient digestibility, T cell phenotypes, and oxidative stress markers. However, energy-corrected milk yield was quadratically increased by CAP, possibly as a result of enhanced mobilization of body fat reserves. In addition, CAP increased neutrophil activity and immune cells related to acute phase immune response.

Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis.

IgA vasculitis (IgAV), previously named as Henoch–Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

Interactions between social behaviour and the acute phase immune response in house finches

In social organisms, immune-mediated behavioural changes (sickness behaviours) can both influence and respond to social dynamics. We tested whether social status in house finches (Haemorhous mexicanus) modulates the acute phase response or aggressive interactions with flockmates. We treated subordinate or dominant finches within captive flocks with lipopolysaccharide (LPS) to stimulate an acute phase response (APR), and quantified mass loss, activity, foraging behaviours, and agonistic interactions. Subordinate finches lost more mass than dominants in response to LPS, but social status did not influence the expression of sickness behaviours (activity and foraging) upon LPS injection. LPS-injected subordinate birds experienced reduced aggression from mid-ranking but not dominant flockmates, indicating status-mediated effects of sickness behaviour on agonistic interactions. Our results suggest that social status in house finches influences one component of the APR (mass loss) and can interact with the APR to modulate intraspecific agonistic interactions in ways likely relevant for disease transmission.

Elevated MBL Levels in Type 1 Diabetic Patients Are Reversed After Simultaneous Pancreas-Kidney Transplantation.

Aim: High levels of circulating Mannan-binding lectin (MBL) are associated with the development of diabetic nephropathy (DN). MBL is an essential component of the acute-phase immune response and initiates the lectin pathway of complement upon binding sugar moieties. In animals, an injurious effect of MBL on diabetic kidney changes has been observed and vasculopathy resulting from hyperglycemia has been shown to be dependent on MBL and lectin complement pathway activation. In humans, the effect of diabetic control on circulating levels of MBL has not been studied so far. Simultaneous pancreas-kidney transplantation (SPK) is an advanced treatment option for type I diabetes (T1D) patients with diabetic nephropathy. By assessing MBL in healthy control subjects and T1D patients before and following SPK, we studied the effect of T1D and SPK on the circulating levels of MBL. Methods: Circulating MBL levels were assessed using sandwich ELISA in plasma of DN (n=21) and SPK patients (n=37), healthy controls (n=19) and DM1 patients (n=15, DM ≥ 40 mL/min). To differentiate between diabetic control and renal failure as possible causes for change in the MBL levels, a subgroup of DN patients receiving a kidney but no pancreas transplant (n=15) were included. In addition, MBL levels were correlated with Hba1c and glucose levels. Results: We found significant elevated levels of MBL in plasma of DN patients compared to healthy controls. MBL levels in DN patients with a normal kidney function were also elevated, although not significant. MBL levels in patients receiving a SPK completely normalized compared to healthy controls. In contrast, MBL levels in DN patient receiving only a kidney transplant remained elevated, suggesting that diabetic control but not reversal of renal failure is associated with a decrease in circulating MBL. In line, glucose levels and Hba1C, but not creatinine levels in DN patients were significantly correlated with levels of MBL. Of interest, we also found a significant correlation between the plasma level of MBL and the duration of T1D before a SPK was needed, suggesting that elevated levels of MBL accelerate the disease progress. Conclusion: In short, we demonstrated that circulating levels of MBL are elevated in DN patients and normalized after SPK. The normalization of MBL levels was independent of renal function, but dependent on diabetic control.

α1-antitrypsin increases interleukin-1 receptor antagonist production during pancreatic islet graft transplantation.

Although islet transplantation for individuals with type 1 diabetes has been shown to yield superior blood glucose control, it remains inadequate for long-term control. This is partly due to islet injuries and stresses that can lead to beta cell loss. Inhibition of excess IL-1β activity might minimize islet injuries, thus preserving function. The IL-1 receptor antagonist (IL-1Ra), an endogenous inhibitor of IL-1β, protects islets from cytokine-induced necrosis and apoptosis. Therefore, an imbalance between IL-1β and IL-1Ra might influence the courses of allogeneic and autoimmune responses to islets. Our group previously demonstrated that the circulating serine-protease inhibitor human alpha-1-antitrypsin (hAAT), the levels of which increase in circulation during acute-phase immune responses, exhibits anti-inflammatory and islet-protective properties, as well as immunomodulatory activity. In the present study, we sought to determine whether the pancreatic islet allograft-protective activity of hAAT was mediated by IL-1Ra induction. Our results demonstrated that hAAT led to a 2.04-fold increase in IL-1Ra expression in stimulated macrophages and that hAAT-pre-treated islet grafts exhibited a 4.851-fold increase in IL-1Ra transcript levels, which were associated with a moderate inflammatory profile. Unexpectedly, islets that were isolated from IL-1Ra-knockout mice and pre-treated with hAAT before grafting into wild-type mice yielded an increase in intragraft IL-1Ra expression that was presumably derived from infiltrating host cells, albeit in the absence of hAAT treatment of the host. Indeed, hAAT-pre-treated islets generated hAAT-free conditioned medium that could induce IL-1Ra production in cultured macrophages. Finally, we demonstrated that hAAT promoted a distinct phosphorylation and nuclear translocation pattern for p65, a key transcription factor required for IL-1Ra expression.

Luminal ATP: the missing link between intestinal alkaline phosphatase, the gut microbiota, and inflammation?

gut dysbiosis is a common feature to many inflammatory diseases but the cause-and-effect relationships between the gut microbiota and host inflammation are poorly understood. For metabolic disorders and obesity, however, bacterial lipopolysaccharide (LPS), an emblematic member of pathogen-associated

A novel hypothesis for an alkaline phosphatase ‘rescue’ mechanism in the hepatic acute phase immune response

The liver isoform of the enzyme alkaline phosphatase (AP) has been used classically as a serum biomarker for hepatic disease states such as hepatitis, steatosis, cirrhosis, drug-induced liver injury, and hepatocellular carcinoma. Recent studies have demonstrated a more general anti-inflammatory role for AP, as it is capable of dephosphorylating potentially deleterious molecules such as nucleotide phosphates, the pathogenic endotoxin lipopolysaccharide (LPS), and the contact clotting pathway activator polyphosphate (polyP), thereby reducing inflammation and coagulopathy systemically. Yet the mechanism underlying the observed increase in liver AP levels in circulation during inflammatory insults is largely unknown. This paper hypothesizes an immunological role for AP in the liver and the potential of this system for damping generalized inflammation along with a wide range of ancillary pathologies. Based on the provided framework, a mechanism is proposed in which AP undergoes transcytosis in hepatocytes from the canalicular membrane to the sinusoidal membrane during inflammation and the enzyme's expression is upregulated as a result. Through a tightly controlled, nucleotide-stimulated negative feedback process, AP is transported in this model as an immune complex with immunoglobulin G by the asialoglycoprotein receptor through the cell and secreted into the serum, likely using the receptor's State 1 pathway. The subsequent dephosphorylation of inflammatory stimuli by AP and uptake of the circulating immune complex by endothelial cells and macrophages may lead to decreased inflammation and coagulopathy while providing an early upstream signal for the induction of a number of anti-inflammatory gene products, including AP itself.

Gene expression responses to Riemerella anatipestifer infection in the liver of ducks

Riemerella anatipestifer is one of the most economically important pathogens of farm ducks worldwide. The molecular mechanisms that underlie its pathogenesis, particularly the host response to R. anatipestifer infection, are poorly understood. The differentially expressed gene profile of duck livers at 24 h following R. anatipestifer infection was therefore investigated using suppression subtractive hybridizaton analysis. A total of 45 differentially expressed genes were identified, which primarily included genes for proteins involved in acute-phase response, inflammatory response, immune response, wound healing and iron homeostasis. For the expression level of 20 genes from those 45 analysed by quantitative reverse transcriptase-polymerase chain reaction at 8, 24 and 48 h post infection, significant differences were observed among the three time points of measurements. The result from this study revealed a gene expression profile of duck liver during R. anatipestifer infection, and those genes with a role in the immune response and wound healing deserving further investigation to elucidate their respective roles during infection.

Flight performance of western sandpipers Calidris mauri remains uncompromised when mounting an acute phase immune response

Migratory birds have been implicated in the spread of some zoonotic diseases, but how well infected individuals can fly remains poorly understood. We used western sandpipers, Calidris mauri, to experimentally test whether flight is affected when long-distance migrants are mounting an immune response and whether migrants maintain immune defences during a flight in a wind tunnel. We measured five indicators of innate immunity in 'flown-healthy' birds (flying in a wind tunnel without mounting an immune response), 'flown-sick' birds (flying while mounting an acute phase response, which is part of induced innate immunity), and a non-flying control group ('not-flown'). Voluntary flight duration did not differ between flown-healthy and flown-sick birds, indicating that mounting an acute phase response to simulated infection did not hamper an individual's ability to fly for up to 3 h. However, in comparison to not-flown birds, bacterial killing ability of plasma was significantly reduced after flight in flown-sick birds. In flown-healthy birds, voluntary flight duration was positively correlated with bacterial killing ability and baseline haptoglobin concentration of the blood plasma measured 1-3 weeks before experimental flights, suggesting that high quality birds had strong immune systems and greater flight capacity. Our findings indicate that flight performance is not diminished by prior immune challenge, but that flight while mounting an acute phase response negatively affects other aspects of immune function. These findings have important implications for our understanding of the transmission of avian diseases, as they suggest that birds can still migrate while fighting an infection.