High interferon type I responses in the lung, plasma and spleen during highly pathogenic H5N1 infection of chicken

This study shows that high pathogenic H5N1 influenza virus infection of chicken induced high levels of bioactive interferon type I in the lung (4.3 × 105 U/mg tissue), plasma (1.1 × 105 U/mL), and spleen (9.1 × 105 U/mg tissue). In contrast, a low pathogenic attenuated H5N1 vaccine strain only induced approximately 24 times less IFN in the lung, 441 times less in the spleen and 649 less in the plasma. This was in the same range as a reassortant carrying the HA from the vaccine strain and the remaining genes from the high pathogenic virus. On the other hand, a reassortant virus with the HA from the high pathogenic H5N1 with the remaining genes from the vaccine strain had intermediate levels of IFN. The level of interferon responses related to the viral load, and those in the spleen and blood to the spread of virus to lymphoid tissue, as well as disease severity. In vitro, the viruses did not induce interferon in chicken embryonic fibroblasts, but high levels in splenocytes, with not clear relationship to pathogenicity and virulence. This, and the responses also with inactivated viruses imply the presence of plasmacytoid dendritic cell-like leukocytes within the chicken immune system, possibly responsible for the high interferon responses during H5N1 infection. Our data also indicate that the viral load as well as the cleavability of the HA enabling systemic spread of the virus are two major factors controlling systemic IFN responses in chicken

Contribution à l'étude des réponses immunitaires cellulaires du porc, par de nouveaux outils méthologiques, dans un modèle d'infection par le virus de la peste porcine classique

RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Membrane markers of the immune cells in swine: an update

Besides their breeding value, swine are increasingly used as biomedical models. As reported in three international swine clusters of differentiation (CD) workshops and in the animal homologue section of the last workshop for the determination of human leukocyte differentiation antigens (HLDA 8), characterisation of leukocyte surface antigens by monoclonal antibodies and other molecular studies have determined the cell lineages and blood leukocyte subsets implicated in the immune response, including cell adhesion molecules involved in cell trafficking. This review focusses on the current state of knowledge of porcine leukocyte differentiation and major histocompatibility complex (SLA) molecules. Examples of porcine particularities such as the double-positive T lymphocytes with the phenotype CD4+CD8low and CD4−CD8low T cell subsets and the persistence of SLA class II after T-lymphocyte activation are illustrated, as well as the shared characteristics of the Artiodactyla group, such as the high proportion of TcR (T cell receptor) T cells in blood and other lymphoid tissues. Furthermore, discrepancies between swine and humans, such as CD16 expression on dendritic cells and CD11b (wCD11R1) tissue distribution are outlined. The rapidly growing information should facilitate manipulation of the swine immune system towards improving disease control, and open new avenues for biomedical research using the pig as a model

The effect on the intestine of some fungal toxins: The Trichothecenes

The intestinal tract represents the first barrier to ingested chemicals or food contaminants and is also the first line of defense against intestinal infection. Because of their location, intestinal epithelial cells could be exposed to high doses of food contaminants. Among natural food contaminants, mycotoxins are regarded as an important risk factor for human and animal health as up to 25% of the world's crop production may be contaminated. The Fusarium genus produces high quantities of toxins (fusariotoxins) in temperate northern countries (North America, Europe or Asia) and the trichothecenes are the most prevalent toxin detected. An increasing number of studies suggest that intestinal epithelial cells are important targets for mycotoxins and in humans, various adverse digestive symptoms are observed on acute exposure. In animals, trichothecenes induce pathological lesions, including necrosis of the intestinal epithelium. They affect the integrity of intestinal epithelium through alterations in the barrier function, cell morphology and differentiation. Moreover these toxins modulate the activity of intestinal epithelium in its role in immune responsiveness. They affect the cytokine production by intestinal or immune cells and are supposed to interfere with the cross-talk between epithelial cells and other intestinal immune cells. This review summarizes our current knowledge of the effects of a class of mycotoxins, the trichothecenes, on the intestine

The fungal T-2 toxin alters the activation of primary macrophages induced by TLR-agonists resulting in a decrease of the inflammatory response in the pig

Abstract T-2 toxin is known to be one of the most toxic trichothecene mycotoxins. Exposure to T-2 toxin induces many hematologic and immunotoxic disorders and is involved in immuno-modulation of the innate immune response. The objective of this work was to evaluate the effects of T-2 toxin on the activation of macrophages by different agonists of Toll-like receptors (TLR) using an in vitro model of primary porcine alveolar macrophages (PAM). Cytotoxic effects of T-2 toxin on PAM were first evaluated. An IC50 of 19.47 ± 0.9753 nM was determined for the cytotoxicity of T-2 toxin. A working concentration of 3 nM of T-2 toxin was chosen to test the effect of T-2 toxin on TLR activation; this dose was not cytotoxic and did not induce apoptosis as demonstrated by Annexin/PI staining. A pre-exposure of macrophages to 3 nM of T-2 toxin decreased the production of inflammatory mediators (IL-1 beta, TNF-alpha, nitric oxide) in response to LPS and FSL1, TLR4 and TLR2/6 agonists respectively. The decrease of the pro-inflammatory response is associated with a decrease of TLR mRNA expression. By contrast, the activation of TLR7 by ssRNA was not modulated by T-2 toxin pre-treatment. In conclusion, our results suggest that ingestion of low concentrations of T-2 toxin affects the TLR activation by decreasing pattern recognition of pathogens and thus interferes with initiation of inflammatory immune response against bacteria and viruses. Consequently, mycotoxins could increase the susceptibility of humans and animals to infectious diseases.</p

Differential influences of the BPA, BPS and BPF on in vitro IL-17 secretion by mouse and human T cells

International audienceThe endocrine disruptor and food contaminant bisphenol A (BPA) is frequently present in consumer plastics and can produce several adverse health effects participating in the development of inflammatory and autoimmune diseases. Regulatory restrictions have been established to prevent risks for human health, leading to the substitution of BPA by structural analogues, such as bisphenol S (BPS) and F (BPF). In this study, we aimed at comparing the in vitro impact of these bisphenols from 0.05 to 50,000 nM on Th17 differentiation, frequency and function in mouse systemic and intestinal immune T cells and in human blood T cells. This study reports the ability of these bisphenols, at low and environmentally relevant concentration, i.e, 0.05 nM, to increase significantly IL-17 production in mouse T cells but not in human T lymphocytes. The use of an aryl hydrocarbon receptor (AhR) specific inhibitor demonstrated its involvement in this bisphenol-induced IL-17 production. We also observed an increased IL-17 secretion by BPS and BPF, and not by BPA, in mouse naive T cells undergoing in vitro Th17 differentiation. In total, this study emphasizes the link between bisphenol exposures and the susceptibility to develop immune diseases, questioning thus the rational of their use to replace BPA

Zymosan-Induced Murine Peritonitis Is Associated with an Increased Sphingolipid Synthesis without Changing the Long to Very Long Chain Ceramide Ratio

Sphingolipids are key molecules in inflammation and defense against pathogens. Their role in dectin-1/TLR2-mediated responses is, however, poorly understood. This study investigated the sphingolipidome in the peritoneal fluid, peritoneal cells, plasma, and spleens of mice after intraperitoneal injection of 0.1 mg zymosan/mouse or PBS as a control. Samples were collected at 2, 4, 8, and 16 h post-injection, using a total of 36 mice. Flow cytometry analysis of peritoneal cells and measurement of IL-6, IL-1β, and TNF-α levels in the peritoneal lavages confirmed zymosan-induced peritonitis. The concentrations of sphingoid bases, dihydroceramides, ceramides, dihydrosphingomyelins, sphingomyelins, monohexosylceramides, and lactosylceramides were increased after zymosan administration, and the effects varied with the time and the matrix measured. The greatest changes occurred in peritoneal cells, followed by peritoneal fluid, at 8 h and 4 h post-injection, respectively. Analysis of the sphingolipidome suggests that zymosan increased the de novo synthesis of sphingolipids without change in the C14–C18:C20–C26 ceramide ratio. At 16 h post-injection, glycosylceramides remained higher in treated than in control mice. A minor effect of zymosan was observed in plasma, whereas sphinganine, dihydrosphingomyelins, and monohexosylceramides were significantly increased in the spleen 16 h post-injection. The consequences of the observed changes in the sphingolipidome remain to be established

Classical Swine Fever Virus Npro Limits Type I Interferon Induction in Plasmacytoid Dendritic Cells by Interacting with Interferon Regulatory Factor 7 ▿

Viruses are detected by different classes of pattern recognition receptors that lead to the activation of interferon regulatory factors (IRF) and consequently to the induction of alpha/beta interferon (IFN-α/β). In turn, efficient viral strategies to escape the type I IFN-induced antiviral mechanisms have evolved. Previous studies established that pestivirus Npro antagonizes the early innate immune response by targeting the transcription factor IRF3 for proteasomal degradation. Here, we report that Npro of classical swine fever virus (CSFV) interacts also with IRF7, another mediator of type I IFN induction. We demonstrate that the Zn-binding domain of Npro is essential for the interaction of Npro with IRF7. For IRF3 and IRF7, the DNA-binding domain, the central region, and most of the regulatory domain are required for the interaction with Npro. Importantly, the induction of IRF7-dependent type I IFN responses in plasmacytoid dendritic cells (pDC) is reduced after wild-type CSFV infection compared with infection with virus mutants unable to interact with IRF7. This is associated with lower levels of IRF7 in pDC. Consequently, wild-type but not Npro mutant CSFV-infected pDC show reduced responses to other stimuli. Taken together, the results of this study show that CSFV Npro is capable of manipulating the function of IRF7 in pDC and provides the virus with an additional strategy to circumvent the innate defense

Transgenerational effects on intestinal inflammation status in mice perinatally exposed to bisphenol S

International audienceIncreasing evidence has highlighted the critical role of early life environment in shaping the future health outcomes of individuals in subsequent generations. Bisphenol S (BPS) has been widely used as a substitute for various plastic materials due to the limited application of Bisphenol A (BPA) which is an endocrine disruptor. However, the lack of efficient evaluation of BPS leaves doubts about the relevant substitute of BPA. Few studies of transgenerational inheritance have examined the effects of environmental exposures to endocrine disruptors on the immune system. In this study, we analyzed the transgenerational effects of BPS on intestinal inflammation and its consequence in metabolism. In this study, only F0 pregnant mice were exposed to BPS (1.5 μg/kg bw/day) from gestational day 0 until weaning of offspring. In this work, both F1 and F2 male offspring developed an inflammatory response in the ileum and colon at adulthood after F0 mothers were exposed to BPS; this phenomenon disappeared in F3. This inflammatory response in F1 male offspring is associated with a significant decrease of blood cholesterol without modification of metabolic status. Further, in F3 offspring male, the decrease of gut inflammatory response is associated with a decrease of fat weight and with an increase of blood glucose and cholesterol level. A sex-specific profile is observed in female offspring. We also observed that early life exposure to BPS was associated with strong abnormal intestinal immune status. The study presented here demonstrates that the immune system, like other organ systems, is vulnerable to transgenerational effects caused by environmental exposure