Interactions hôtes-agents pathogènes

BACKGROUND AND AIMS: Early endoscopic recurrence is frequent after intestinal resection for Crohn's disease. Bacteria are involved, and probiotics may modulate immune responses to the intestinal flora. Here we tested the probiotic strain Lactobacillus johnsonii LA1 in this setting. PATIENTS AND METHODS: This was a randomised, double blind, placebo controlled study. Patients were eligible if they had undergone surgical resection of <1 m, removing all macroscopic lesions within the past 21 days. Patients were randomised to receive two packets per day of lyophilised LA1 (2 x 10(9) cfu) or placebo for six months; no other treatment was allowed. The primary endpoint was endoscopic recurrence at six months, with grade >1 in Rutgeerts' classification or an adapted classification for colonic lesions. Endoscopic score was the maximal grade of ileal and colonic lesions. Analyses were performed primarily on an intent to treat basis. RESULTS: Ninety eight patients were enrolled (48 in the LA1 group). At six months, endoscopic recurrence was observed in 30/47 patients (64%) in the placebo group and in 21/43 (49%) in the LA1 group (p = 0.15). Per protocol analysis confirmed this result. Endoscopic score distribution did not differ significantly between the LA1 and placebo groups. There were four clinical recurrences in the LA1 group and three in the placebo group. CONCLUSION: L johnsonii LA1 (4 x 10(9) cfu/day) did not have a sufficient effect, if any, to prevent endoscopic recurrence of Crohn's disease.

Novel species of fungi described in this study include those from various countries as follows: Australia : Apiognomonia lasiopetali on Lasiopetalum sp., Blastacervulus eucalyptorum on Eucalyptus adesmophloia , Bullanockia australis (incl. Bullanockia gen. nov.) on Kingia australis , Caliciopsis eucalypti on Eucalyptus marginata , Celerioriella petrophiles on Petrophile teretifolia , Coleophoma xanthosiae on Xanthosia rotundifolia , Coniothyrium hakeae on Hakea sp., Diatrypella banksiae on Banksia formosa , Disculoides corymbiae on Corymbia calophylla , Elsinoë eelemani on Melaleuca alternifolia , Elsinoë eucalyptigena on Eucalyptus kingsmillii , Elsinoë preissianae on Eucalyptus preissiana , Eucasphaeria rustici on Eucalyptus creta , Hyweljonesia queenslandica (incl. Hyweljonesia gen. nov.) on the cocoon of an unidentified microlepidoptera, Mycodiella eucalypti (incl. Mycodiella gen. nov.) on Eucalyptus diversicolor , Myrtapenidiella sporadicae on Eucalyptus sporadica , Neocrinula xanthorrhoeae (incl. Neocrinula gen. nov.) on Xanthorrhoea sp., Ophiocordyceps nooreniae on dead ant, Phaeosphaeriopsis agavacearum on Agave sp., Phlogicylindrium mokarei on Eucalyptus sp., Phyllosticta acaciigena on Acacia suaveolens , Pleurophoma acaciae on Acacia glaucoptera , Pyrenochaeta hakeae on Hakea sp., Readeriella lehmannii on Eucalyptus lehmannii , Saccharata banksiae on Banksia grandis , Saccharata daviesiae on Daviesia pachyphylla , Saccharata eucalyptorum on Eucalyptus bigalerita , Saccharata hakeae on Hakea baxteri , Saccharata hakeicola on Hakea victoria , Saccharata lambertiae on Lambertia ericifolia , Saccharata petrophiles on Petrophile sp., Saccharata petrophilicola on Petrophile fastigiata , Sphaerellopsis hakeae on Hakea sp., and Teichospora kingiae on Kingia australis . Brazil : Adautomilanezia caesalpiniae (incl. Adautomilanezia gen. nov.) on Caesalpina echinata , Arthrophiala arthrospora (incl. Arthrophiala gen. nov.) on Sagittaria montevidensis , Diaporthe caatingaensis (endophyte from Tacinga inamoena ), Geastrum ishikawae on sandy soil, Geastrum pusillipilosum on soil, Gymnopus pygmaeus on dead leaves and sticks, Inonotus hymenonitens on decayed angiosperm trunk, Pyricularia urashimae on Urochloa brizantha , and Synnemellisia aurantia on Passiflora edulis . Chile : Tubulicrinis australis on Lophosoria quadripinnata . France : Cercophora squamulosa from submerged wood, and Scedosporium cereisporum from fluids of a wastewater treatment plant. Hawaii : Beltraniella acaciae , Dactylaria acaciae , Rhexodenticula acaciae , Rubikia evansii and Torula acaciae (all on Acacia koa ). India : Lepidoderma echinosporum on dead semi-woody stems, and Rhodocybe rubrobrunnea from soil. Iran : Talaromyces kabodanensis from hypersaline soil. La Réunion : Neocordana musarum from leaves of Musa sp. Malaysia : Anungitea eucalyptigena on Eucalyptus grandis × pellita , Camptomeriphila leucaenae (incl. Camptomeriphila gen. nov.) on Leucaena leucocephala , Castanediella communis on Eucalyptus pellita , Eucalyptostroma eucalypti (incl. Eucalyptostroma gen. nov.) on Eucalyptus pellita , Melanconiella syzygii on Syzygium sp., Mycophilomyces periconiae (incl. Mycophilomyces gen. nov.) as hyperparasite on Periconia on leaves of Albizia falcataria , Synnemadiella eucalypti (incl. Synnemadiella gen. nov.) on Eucalyptus pellita , and Teichospora nephelii on Nephelium lappaceum . Mexico : Aspergillus bicephalus from soil. New Zealand : Aplosporella sophorae on Sophora microphylla , Libertasomyces platani on Platanus sp., Neothyronectria sophorae (incl. Neothyronectria gen. nov.) on Sophora microphylla , Parastagonospora phoenicicola on Phoenix canariensis , Phaeoacremonium pseudopanacis on Pseudopanax crassifolius , Phlyctema phoenicis on Phoenix canariensis , and Pseudoascochyta novae-zelandiae on Cordyline australis . Panama : Chalara panamensis from needle litter of Pinus cf. caribaea . South Africa : Exophiala eucalypti on leaves of Eucalyptus sp., Fantasmomyces hyalinus (incl. Fantasmomyces gen. nov.) on Acacia exuvialis , Paracladophialophora carceris (incl. Paracladophialophora gen. nov.) on Aloe sp., and Umthunziomyces hagahagensis (incl. Umthunziomyces gen. nov.) on Mimusops caffra . Spain : Clavaria griseobrunnea on bare ground in Pteridium aquilinum field, Cyathus ibericus on small fallen branches of Pinus halepensis , Gyroporus pseudolacteus in humus of Pinus pinaster , and Pseudoascochyta pratensis (incl. Pseudoascochyta gen. nov.) fromsoil. Thailand : Neoascochyta adenii on Adenium obesum , and Ochroconis capsici on Capsicum annuum . UK : Fusicolla melogrammae from dead stromata of Melogramma campylosporum on bark of Carpinus betulus . Uruguay : Myrmecridium pulvericola from house dust. USA : Neoscolecobasidium agapanthi (incl. Neoscolecobasidium gen. nov.) on Agapanthus sp., Polyscytalum purgamentum on leaf litter, Pseudopithomyces diversisporus from human

Of the Orthomyxoviridae family of viruses, only influenza A viruses are thought to exist as multiple subtypes and has non-human maintenance hosts. In April 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. Subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven RNA segments exhibiting approximately 50% overall amino acid identity to human influenza C virus. Based on its genetic organizational similarities to influenza C viruses this virus has been provisionally designated C/Oklahoma/1334/2011 (C/OK). Phylogenetic analysis of the predicted viral proteins found that the divergence between C/OK and human influenza C viruses was similar to that observed between influenza A and B viruses. No cross reactivity was observed between C/OK and human influenza C viruses using hemagglutination inhibition (HI) assays. Additionally, screening of pig and human serum samples found that 9.5% and 1.3%, respectively, of individuals had measurable HI antibody titers to C/OK virus. C/OK virus was able to infect both ferrets and pigs and transmit to naive animals by direct contact. Cell culture studies showed that C/OK virus displayed a broader cellular tropism than a human influenza C virus. The observed difference in cellular tropism was further supported by structural analysis showing that hemagglutinin esterase (HE) proteins between two viruses have conserved enzymatic but divergent receptor-binding sites. These results suggest that C/OK virus represents a new subtype of influenza C viruses that currently circulates in pigs that has not been recognized previously. The presence of multiple subtypes of co-circulating influenza C viruses raises the possibility of reassortment and antigenic shift as mechanisms of influenza C virus evolution.

Mention d'édition : 3rd ed.

Many studies have shown that subclinical ketosis (SCK) is associated with an increased risk of developing various diseases, reproductive disorders, and changes in milk production. The present work aims at producing an overview between this disorder and theses outcomes. A meta-analysis of the literature, including 131 different models from 23 papers, or a review when the literature was scarce was conducted. For each outcome, the odds ratio (OR), relative risk, or hazard ratio was presented for various moderators to reduce heterogeneity among the studies. The raw change in milk production associated with SCK was estimated and adjusted, taking into consideration the outcomes known to interact with milk production during the peripartum period. The results showed that 2 main categories of moderators had a significant effect on the adjusted risk. First, the adjustment made by defining SCK as (1) β-hydroxybutyrate concentration >1.4 mM, (2) nonesterified fatty acid (NEFA) concentration >0.4 mM prepartum, or (3) NEFA concentration >1.0 mM postpartum corrected the underestimated risk (despite low significance). This is because several trials reported the relevant risks using lower thresholds for the β-hydroxybutyrate or NEFA values. Using a low threshold leads to lower risk of disease compared with using a high threshold. Second, the correction produced using the polyfactorial terms corrected the overestimation of risk because many trials reported only univariable models. The relative risk or OR (95% confidence interval) related to abomasal displacement, clinical ketosis, early culling and death, metritis, placental retention, clinical mastitis, lameness, and a doubling of the SCC in cases with SCK were 3.33 (2.60-4.25), 5.38 (3.27-8.83), 1.92 (1.60-2.30), 1.75 (1.54-2.01), 1.52 (1.20-1.93), 1.61 (1.24-2.09), 2.01(1.64-2.44), and 1.42 (1.26-1.60), respectively. The precision level of the estimate depended on the outcome. The direct mean ± standard deviation of the 305-d milk losses associated with SCK were 251 ± 73 kg after adjusting for abomasal displacement, clinical ketosis, metritis, and placental retention. The OR (95% confidence interval) for first service calving risk in cases of SCK was 0.67 (0.53-0.83). The calving-to-first-service interval was 8 d longer and the calving-to-conception interval was 16 to 22 d longer in cows with SCK. The relationships among the different reproductive indicators were quantified in only 1 or 2 trials. The present work highlights the need to conduct further studies on the associations between SCK and the risks of diseases, changes in milk production, and reproductive parameters.

The ubiquitin-proteasome pathway regulates gene expression through protein degradation. Here we show that the F-box protein betaTrCP, the receptor component of the SCF E3 ubiquitin ligase responsible for IkappaBalpha and beta-catenin degradation, is colocalized in the nucleus with ATF4, a member of the ATF-CREB bZIP family of transcription factors, and controls its stability. Association between the two proteins depends on ATF4 phosphorylation and on ATF4 serine residue 219 present in the context of DSGXXXS, which is similar but not identical to the motif found in other substrates of betaTrCP. ATF4 ubiquitination in HeLa cells is enhanced in the presence of betaTrCP. The F-box-deleted betaTrCP protein behaves as a negative transdominant mutant that inhibits ATF4 ubiquitination and degradation and, subsequently, enhances its activity in cyclic AMP-mediated transcription. ATF4 represents a novel substrate for the SCF(betaTrCP) complex, which is the first mammalian E3 ubiquitin ligase identified so far for the control of the degradation of a bZIP transcription factor.

Protein folding homeostasis in the lumen of the endoplasmic reticulum is defended by signal transduction pathways that are activated by an imbalance between unfolded proteins and chaperones (so called ER stress). Collectively referred to as the unfolded protein response (UPR) this homeostatic response is initiated by three known ER stress transducers: IRE1, PERK and ATF6. These ER-localised transmembrane (TM) proteins posses lumenal stress sensing domains and cytosolic effector domains that collectively activate a gene expression programme regulating the production of proteins involved in the processing and maturation of secreted proteins that enter the ER. However, beyond limiting unfolded protein stress in the ER the UPR has important connections to lipid metabolism that are the subject of this review.

Condensed tannins (CTs) account for up to 20% of the dry matter in forage legumes used as ruminant feeds. Beneficial animal responses to CTs have included improved growth, milk and wool production, fertility, and reduced methane emissions and ammonia volatilization from dung or urine. Most important is the ability of such forages to combat the effects of gastrointestinal parasitic nematodes. Inconsistent animal responses to CTs were initially attributed to concentration in the diet, but recent research has highlighted the importance of their molecular structures, as well as concentration, and also the composition of the diet containing the CTs. The importance of CT structural traits cannot be underestimated. Interdisciplinary research is the key to unraveling the relationships between CT traits and bioactivities and will enable future on‐farm exploitation of these natural plant compounds. Research is also needed to provide plant breeders with guidelines and screening tools to optimize CT traits, in both the forage and the whole diet. In addition, improvements are needed in the competitiveness and agronomic traits of CT‐containing legumes and our understanding of options for their inclusion in ruminant diets. Farmers need varieties that are competitive in mixed swards and have predictable bioactivities. This review covers recent results from multidisciplinary research on sainfoin ( Onobrychis Mill. spp.) and provides an overview of current developments with several other tanniniferous forages. Tannin chemistry is now being linked with agronomy, plant breeding, animal nutrition, and parasitology. The past decade has yielded considerable progress but also generated more questions—an enviable consequence of new knowledge!

Mastitis caused by Escherichia coli and Staphylococcus aureus is a major pathology of dairy cows. To better understand the differential response of the mammary gland to these two pathogens, we stimulated bovine mammary epithelial cells (bMEC) with either E. coli crude lipopolysaccharide (LPS) or with S. aureus culture supernatant (SaS) to compare the transcriptomic profiles of the initial bMEC response. By using HEK 293 reporter cells for pattern recognition receptors, the LPS preparation was found to stimulate TLR2 and TLR4 but not TLR5, Nod1 or Nod2, whereas SaS stimulated TLR2. Biochemical analysis revealed that lipoteichoic acid, protein A and α-hemolysin were all present in SaS, and bMEC were found to be responsive to each of these molecules. Transcriptome profiling revealed a core innate immune response partly shared by LPS and SaS. However, LPS induced expression of a significant higher number of genes and the fold changes were of greater magnitude than those induced by SaS. Microarray data analysis suggests that the activation pathways and the early chemokine and cytokine production preceded the defense and stress responses. A major differential response was the activation of the type I IFN pathway by LPS but not by SaS. The higher upregulation of chemokines (Cxcl10, Ccl2, Ccl5 and Ccl20) that target mononuclear leucocytes by LPS than by SaS is likely to be related to the differential activation of the type I IFN pathway, and could induce a different profile of the initial recruitment of leucocytes. The MEC responses to the two stimuli were different, as LPS was associated with NF-κB and Fas signaling pathways, whereas SaS was associated with AP-1 and IL-17A signaling pathways. It is noteworthy that at the protein level secretion of TNF-α and IL-1β was not induced by either stimulus. These results suggest that the response of MEC to diffusible stimuli from E. coli and S. aureus contributes to the onset of the response with differential leucocyte recruitment and distinct inflammatory and innate immune reactions of the mammary gland to infection.

This study assessed knowledge gaps and suggested research priorities in the field of Staphylococcus aureus mastitis. Staphylococcus aureus infecting the mammary gland remains a major problem to the dairy industry worldwide because of its pathogenicity, contagiousness, persistence in the cow environment, colonization of skin or mucosal epithelia, and the poor curing efficacy of treatments. Staphylococcus aureus also constitutes a threat to public health due to food safety and antibiotic usage issues and the potential for bidirectional transmission of strains between humans and dairy animals (cows and small ruminants). Gaps have been identified in (i) understanding the molecular basis for pathogenesis of S. aureus mastitis, (ii) identifying staphylococcal antigens inducing protection and (iii) determining the cell-mediated immune responses to infection and vaccination. The recommended priorities for research are (i) improved diagnostic methods for early detection of infection and intervention through treatment or management, (ii) development of experimental models to investigate the strategies used by S. aureus to survive within the mammary gland and resist treatment with anti-microbials, (iii) investigation of the basis for cow-to-cow variation in response to S. aureus mastitis, (iv) identification of the immune responses (adaptive and innate) induced by infection or vaccination and (v) antibacterial discovery programmes to develop new, more effective, narrow spectrum antibacterial agents for the treatment of S. aureus mastitis. With the availability and ongoing improvement of molecular research tools, these objectives may not be out of reach in the future.

Enteropathogenic Escherichia coli (EPEC) is a causative agent of infant diarrhoea in developing countries. The EspF protein is the product of the espF gene found on the locus of enterocyte effacement, the key pathogenicity island carried by EPEC and enterohemorrhagic E. coli. EspF is injected from adherent EPEC into host cells via a type III secretion system and was previously shown to induce apoptotic cell death and to be required for disruption of host intestinal barrier function. In this work, we show by immunofluorescence and fractionation studies that EspF is targeted to host mitochondria. The N-terminal region of EspF serves as a mitochondrial import signal and, when expressed within cells, can target hybrid green fluorescent protein to mitochondria. Assessment of mitochondrial membrane potential in infected epithelial cells indicated that EspF plays a role in the mitochondrial membrane permeabilization induced by EPEC infection. Furthermore, EspF was associated with the release of cytochrome c from mitochondria into the cytoplasm and with caspase-9 and caspase-3 cleavage. These findings indicate a role for EspF in initiating the mitochondrial death pathway.

Low colostrum intake at birth results in the failure of passive transfer (FPT) due to the inadequate ingestion of colostral immunoglobulins (Ig). FPT is associated with an increased risk of mortality and decreased health and longevity. Despite the known management practices associated with low FPT, it remains an important issue in the field. Neither a quantitative analysis of FPT consequences nor an assessment of its total cost are available. To address this point, a meta-analysis on the adjusted associations between FPT and its outcomes was first performed. Then, the total costs of FPT in European systems were calculated using a stochastic method with adjusted values as the input parameters. The adjusted risks (and 95% confidence intervals) for mortality, bovine respiratory disease, diarrhoea and overall morbidity in the case of FPT were 2.12 (1.43-3.13), 1.75 (1.50-2.03), 1.51 (1.05-2.17) and 1.91 (1.63-2.24), respectively. The mean (and 95% prediction interval) total costs per calf with FPT were estimated to be €60 (€10-109) and €80 (€20-139) for dairy and beef, respectively. As a result of the double-step stochastic method, the proposed economic estimation constitutes the first estimate available for FPT. The results are presented in a way that facilitates their use in the field and, with limited effort, combines the cost of each contributor to increase the applicability of the economic assessment to the situations farm-advisors may face. The present economic estimates are also an important tool to evaluate the profitability of measures that aim to improve colostrum intake and FPT prevention.

Diets rich in saturated fatty acids (SFAs) produce a form of tissue inflammation driven by "metabolically activated" macrophages. We show that SFAs, when in excess, induce a unique transcriptional signature in both mouse and human macrophages that is enriched by a subset of ER stress markers, particularly IRE1α and many adaptive downstream target genes. SFAs also activate the NLRP3 inflammasome in macrophages, resulting in IL-1β secretion. We found that IRE1α mediates SFA-induced IL-1β secretion by macrophages and that its activation by SFAs does not rely on unfolded protein sensing. We show instead that the ability of SFAs to stimulate either IRE1α activation or IL-1β secretion can be specifically reduced by preventing their flux into phosphatidylcholine (PC) or by increasing unsaturated PC levels. Thus, IRE1α is an unrecognized intracellular PC sensor critical to the process by which SFAs stimulate macrophages to secrete IL-1β, a driver of diet-induced tissue inflammation.

The cytoplasmic domains of the transmembrane (TM) envelope proteins (TM-CDs) of most retroviruses have a Tyr-based motif, YXXO, in their membrane-proximal regions. This signal is involved in the trafficking and endocytosis of membrane receptors via clathrin-associated AP-1 and AP-2 adaptor complexes. We have used CD8-TM-CD chimeras to investigate the role of the Tyr-based motif of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and human T-leukemia virus type 1 (HTLV-1) TM-CDs in the cell surface expression of the envelope glycoprotein. Flow cytometry and confocal microscopy studies showed that this motif is a major determinant of the cell surface expression of the CD8-HTLV chimera. The YXXO motif also plays a key role in subcellular distribution of the envelope of lentiviruses HIV-1 and SIV. However, these viruses, which encode TM proteins with a long cytoplasmic domain, have additional determinants distal to the YXXO motif that participate in regulating cell surface expression. We have also used the yeast two-hybrid system and in vitro binding assays to demonstrate that all three retroviral YXXO motifs interact with the micro1 and micro2 subunits of AP complexes and that the C-terminal regions of HIV-1 and SIV TM proteins interact with the beta2 adaptin subunit. The TM-CDs of HTLV-1, HIV-1, and SIV also interact with the whole AP complexes. These results clearly demonstrate that the cell surface expression of retroviral envelope glycoproteins is governed by interactions with adaptor complexes. The YXXO-based signal is the major determinant of this interaction for the HTLV-1 TM, which contains a short cytoplasmic domain, whereas the lentiviruses HIV-1 and SIV have additional determinants distal to this signal that are also involved.

Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually. The unusually low permeability of its cell wall contributes to the ability of M. tuberculosis to grow within host macrophages, a property required for pathogenesis of infection. Mycobacterium marinum is an established model for discovering genes involved in mycobacterial infection. Mycobacterium marinum mutants with transposon insertions in the beta-ketoacyl-acyl carrier protein synthase B gene (kasB) grew poorly in macrophages, although growth in vitro was unaffected. Detailed analyses by thin-layer chromatography, nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, infrared spectroscopy, and chemical degradations showed that the kasB mutants synthesize mycolic acids that are 2-4 carbons shorter than wild type; the defect was localized to the proximal portion of the meromycolate chain. In addition, these mutants showed a significant (approximately 30%) reduction in the abundance of keto-mycolates, with a slight compensatory increase of both alpha- and methoxy-mycolates. Despite these small changes in mycolate length and composition, the kasB mutants exhibited strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensin and lysozyme. The abnormalities of the kasB mutants were fully complemented by expressing M. tuberculosis kasB, but not by the closely related gene kasA. These studies identify kasB as a novel target for therapeutic intervention in mycobacterial diseases.

A new influenza virus, genus D, isolated in US pigs and cattle, has also been circulating in cattle in France. It was first identified there in 2011, and an increase was detected in 2014. The virus genome in France is 94%-99% identical to its US counterpart, which suggests intercontinental spillover.

RATIONALE: The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown. OBJECTIVES: To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza. METHODS: We used targeted gene deletion approaches and pharmacologic interventions to investigate the role of platelets during influenza virus infection in mice. MEASUREMENTS AND MAIN RESULTS: Lungs of infected mice were massively infiltrated by aggregates of activated platelets. Platelet activation promoted influenza A virus pathogenesis. Activating protease-activated receptor 4, a platelet receptor for thrombin that is crucial for platelet activation, exacerbated influenza-induced acute lung injury and death. In contrast, deficiency in the major platelet receptor glycoprotein IIIa protected mice from death caused by influenza viruses, and treating the mice with a specific glycoprotein IIb/IIIa antagonist, eptifibatide, had the same effect. Interestingly, mice treated with other antiplatelet compounds (antagonists of protease-activated receptor 4, MRS 2179, and clopidogrel) were also protected from severe lung injury and lethal infections induced by several influenza strains. CONCLUSIONS: The intricate relationship between hemostasis and inflammation has major consequences in influenza virus pathogenesis, and antiplatelet drugs might be explored to develop new antiinflammatory treatment against influenza virus infections.

CD47 on the surface of T cells was shown in vitro to mediate either T cell activation or, in the presence of high amounts of thrombospondin (TSP), T cell apoptosis. We report here that CD47-deficient mice, as well as TSP-1 or TSP-2-deficient mice, sustain oxazolone-induced inflammation for more than four days, whereas wild-type mice reduce the inflammation within 48 h. We observe that prolonged inflammation in CD47-, TSP-1-, or TSP-2-deficient mice is accompanied by a local deficiency of T cell apoptosis. Finally, we show that upon activation normal T cells increase the expression of the proapoptotic Bcl-2 family member BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) and undergo CD47-mediated apoptosis. This finding is consistent with our previous demonstration of a physical interaction between BNIP3 and CD47 that inhibits BNIP3 degradation by the proteasome, sensitizing T cells to CD47-induced apoptosis. Overall, these results reveal an important role in vivo for this new CD47/BNIP3 pathway in limiting inflammation by controlling the number of activated T cells.

A cross-sectional study based on a questionnaire survey was conducted to determine the distribution of lumpy skin disease (LSD) and associated risk factors in three main agro-climatic zones of Ethiopia. A total of 330 questionnaire surveys were collected from 44 peasant associations (PA) distributed in 15 districts. Across agro-climate zones, herd-level LSD prevalence in the midland agro-climate was significantly higher 55.2% [95% confidence interval (CI) 47.5-62.6] than in highland and lowland agro-climate zones. Overall observed LSD prevalence at animal-level was 8.1% (95% CI 7.3-8.9) and observed mortality was 2.12% (95% CI 1.73-2.6). The odds ratio (OR) of LSD occurrence in midland vs. highland and lowland vs. highland zones was 3.86 (95% CI 2.61-5.11) and 4.85 (95% CI 2.59-7.1), respectively. Significantly high risk of LSD occurrence was associated with communal grazing and watering management (OR 4.1, 95% CI 2.02-6.18) and introduction of new cattle (OR 8.5, 95% CI 6.0-11.0). Our findings describe the distribution of LSD in different agro-climates in Ethiopia along with associated risk factors, and can help shed light on the epidemiology of LSD in other African countries suffering from the disease.

The objective of the present report was to review briefly the potentially community-acquired Acinetobacter baumannii infections, to update information on the reservoirs of A. baumannii outside the hospital, and to consider their potential interactions with human infections. Most reports on potentially community-acquired A. baumannii have been published during the last 15 years. They concern community-acquired pneumonia, infections in survivors from natural disasters, and infected war wounds in troops from Iraq and Afghanistan. Although the existence of extra-hospital reservoirs of A. baumannii has long been disputed, the recent implementation of molecular methods has allowed the demonstration of the actual presence of this organism in various environmental locations, in human carriage, in pets, slaughter animals, and human lice. Although the origin of the A. baumannii infections in soldiers injured in Southwestern Asia is difficult to determine, there are some arguments to support the involvement of extra-hospital reservoirs in the occurrence of community-acquired infections. Overall, the emergence of community-acquired A. baumannii infections could be associated with interactions between animals, environment, and humans that are considered to be potentially involved in the emergence or re-emergence of some infectious diseases.