scholarly journals Variation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdom

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Kirsty Jensen ◽  
Iain J. Gallagher ◽  
Nicholas Johnston ◽  
Michael Welsh ◽  
Robin Skuce ◽  
...  

ABSTRACT Bovine tuberculosis has been an escalating animal health issue in the United Kingdom since the 1980s, even though control policies have been in place for over 60 years. The importance of the genetics of the etiological agent, Mycobacterium bovis , in the reemergence of the disease has been largely overlooked. We compared the interaction between bovine monocyte-derived macrophages (bMDM) and two M. bovis strains, AF2122/97 and G18, representing distinct genotypes currently circulating in the United Kingdom. These M. bovis strains exhibited differences in survival and growth in bMDM. Although uptake was similar, the number of viable intracellular AF2122/97 organisms increased rapidly, while G18 growth was constrained for the first 24 h. AF2122/97 infection induced a greater transcriptional response by bMDM than G18 infection with respect to the number of differentially expressed genes and the fold changes measured. AF2122/97 infection induced more bMDM cell death, with characteristics of necrosis and apoptosis, more inflammasome activation, and a greater type I interferon response than G18. In conclusion, the two investigated M. bovis strains interact in significantly different ways with the host macrophage. In contrast to the relatively silent infection by G18, AF2122/97 induces greater signaling to attract other immune cells and induces host cell death, which may promote secondary infections of naive macrophages. These differences may affect early events in the host-pathogen interaction, including granuloma development, which could in turn alter the progression of the disease. Therefore, the potential involvement of M. bovis genotypes in the reemergence of bovine tuberculosis in the United Kingdom warrants further investigation.

2014 ◽  
Vol 82 (5) ◽  
pp. 2068-2078 ◽  
Author(s):  
Christopher R. Doyle ◽  
Ji-An Pan ◽  
Patricio Mena ◽  
Wei-Xing Zong ◽  
David G. Thanassi

ABSTRACTFrancisella tularensisis a facultative intracellular, Gram-negative pathogen and the causative agent of tularemia. We previously identified TolC as a virulence factor of theF. tularensislive vaccine strain (LVS) and demonstrated that a ΔtolCmutant exhibits increased cytotoxicity toward host cells and elicits increased proinflammatory responses compared to those of the wild-type (WT) strain. TolC is the outer membrane channel component used by the type I secretion pathway to export toxins and other bacterial virulence factors. Here, we show that the LVS delays activation of the intrinsic apoptotic pathway in a TolC-dependent manner, both during infection of primary macrophages and during organ colonization in mice. The TolC-dependent delay in host cell death is required forF. tularensisto preserve its intracellular replicative niche. We demonstrate that TolC-mediated inhibition of apoptosis is an active process and not due to defects in the structural integrity of the ΔtolCmutant. These findings support a model wherein the immunomodulatory capacity ofF. tularensisrelies, at least in part, on TolC-secreted effectors. Finally, mice vaccinated with the ΔtolCLVS are protected from lethal challenge and clear challenge doses faster than WT-vaccinated mice, demonstrating that the altered host responses to primary infection with the ΔtolCmutant led to altered adaptive immune responses. Taken together, our data demonstrate that TolC is required for temporal modulation of host cell death during infection byF. tularensisand highlight how shifts in the magnitude and timing of host innate immune responses may lead to dramatic changes in the outcome of infection.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Agnese Rondoni ◽  
Elena Millan ◽  
Daniele Asioli

PurposePlant-based eggs have recently been developed to provide consumers with a healthier, animal-friendlier and more sustainable alternative to conventional eggs. The purpose of this paper is to investigate intrinsic and extrinsic attribute preferences for three prototypes of plant-based egg, namely the liquid, powder and egg-shaped.Design/methodology/approachNine focus groups in the United Kingdom and nine in Italy were conducted, with a total of 180 participants. A thematic analysis of results was conducted.FindingsIn terms of intrinsic product attributes, consumers' preferences for colour, shape, taste, ingredients, nutrients, method of production and shelf-life for plant-based eggs were revealed. Regarding the extrinsic attributes, preferences for price, packaging, country of origin and product naming emerged. Similarities and differences between consumers from the two countries are also discussed. Differences in preferences also emerged between vegan and non-vegan consumers.Research limitations/implicationsThis study adds to the existing knowledge on consumers' preferences for new plant-based food alternatives and identifies future quantitative approaches based on qualitative findings.Practical implicationsResults from this study can assist plant-based egg manufacturers in improving their products in line with consumers' expectations, which may help reducing risk of product failure.Originality/valueThis study is the first to investigate consumers' preferences, expectations and needs for new food products like plant-based eggs and provides information that can be practically applied by manufacturers, as well as suggestions for future research.


2018 ◽  
Vol 84 (14) ◽  
Author(s):  
Lydia J. Leon ◽  
Ronan Doyle ◽  
Ernest Diez-Benavente ◽  
Taane G. Clark ◽  
Nigel Klein ◽  
...  

ABSTRACT In this study, differences in the placental microbiota from term and preterm deliveries in a large pregnancy cohort in the United Kingdom were studied by using 16S-targeted amplicon sequencing. The impacts of contamination from DNA extraction, PCR reagents, and the delivery itself were also examined. A total of 400 placental samples from 256 singleton pregnancies were analyzed, and differences between spontaneous preterm-, nonspontaneous preterm-, and term-delivered placentas were investigated. DNA from recently delivered placentas was extracted, and screening for bacterial DNA was carried out by using targeted sequencing of the 16S rRNA gene on the Illumina MiSeq platform. Sequenced reads were analyzed for the presence of contaminating operational taxonomic units (OTUs) identified via sequencing of negative extraction and PCR-blank samples. Differential abundances and between-sample (beta) diversity metrics were then compared. A large proportion of the reads sequenced from the extracted placental samples mapped to OTUs that were also found for negative extractions. Striking differences in the compositions of samples were also observed, according to whether the placenta was delivered abdominally or vaginally, providing strong circumstantial evidence for delivery contamination as an important contributor to observed microbial profiles. When OTU- and genus-level abundances were compared between the groups of interest, a number of organisms were enriched in the spontaneous preterm-delivery cohort, including organisms that have been associated previously with adverse pregnancy outcomes, specifically Mycoplasma spp. and Ureaplasma spp. However, analyses of the overall community structure did not reveal convincing evidence for the existence of a reproducible “preterm placental microbiome.” IMPORTANCE Preterm birth is associated with both psychological and physical disabilities and is the leading cause of infant morbidity and mortality worldwide. Infection is known to be an important cause of spontaneous preterm birth, and recent research has implicated variation in the “placental microbiome” in the risk of preterm birth. Consistent with data from previous studies, the abundances of certain clinically relevant species differed between spontaneous preterm- and nonspontaneous preterm- or term-delivered placentas. These results support the view that a proportion of spontaneous preterm births have an intrauterine-infection component. However, an additional observation from this study was that a substantial proportion of sequenced reads were contaminating reads rather than DNA from endogenous, clinically relevant species. This observation warrants caution in the interpretation of sequencing outputs from low-biomass samples such as the placenta.


Significance The United Kingdom eyes a strategic tilt to the Indo-Pacific, with South-east Asia a key focus because of its economic dynamism and the convening power of ASEAN. The aircraft carrier HMS Queen Elizabeth will deploy to the Indo-Pacific for six months later this year. Impacts The United Kingdom’s view of China as a systemic challenger makes a trade pact between the two countries unlikely. UK efforts to conclude a trade deal with India will be frustrated by Delhi’s protectionist approach. London will pursue closer defence cooperation with Tokyo.


Significance All three countries are united by the objective to mitigate US-China rivalry by promoting multilateralism and engagement among middle powers, while at the same time using these to contain China’s behaviour and ambitions in the region. Impacts Engaging with like-minded middle powers in the Indo-Pacific will help Europe distance itself from Washington’s tougher policy on China. The Indo-Pacific vision will result in deepening defence partnerships with India, plus Australia and Japan, such as through arms sales. The Indo-Pacific will be an area of potential future collaboration and cooperation between the United Kingdom and EU countries.


Significance However, there has been a notable change in the EU’s tone. In July, the European Commission unexpectedly paused legal action against the United Kingdom for an alleged breach of the NIP, and when London announced on September 6 that it was suspending key elements indefinitely, the EU’s response was muted. Impacts France is so deeply aggrieved over AUKUS that any further UK breaches of the Withdrawal Agreement could prompt a bad-tempered response. The possibility of an early assembly election in Northern Ireland would complicate EU-UK attempts to resolve the NIP issue. The exclusion of high profile, pro-EU politicians in the UK cabinet reshuffle shows how important the Brexit agenda remains for London.


2020 ◽  
Vol 22 (3) ◽  
pp. 233-245
Author(s):  
Yasmine Dominguez-Whitehead ◽  
Felix Maringe

PurposeThis paper provides a cross-national analysis of PhD supervision models, milestones and examination procedures in order to compare PhD programs and their practices.Design/methodology/approachA comparative approach is employed, which systematically interrogates PhD supervision models, milestones and examination procedures in the United Kingdom, South Africa and the United States via a comprehensive review of the practices and literature.FindingsThe findings indicate the ramifications of the different approaches and highlight the benefits and drawbacks associated with the different models.Originality/valueBy making explicit the dominant supervision models, milestones and examination procedures that exist in the United Kingdom, South Africa and the United States, the authors shed light on the somewhat obscure path to earning a PhD degree.


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