Tracey Coffey - Academia.edu (original) (raw)

Papers by Tracey Coffey

Pathogens

Streptococcus uberis is a common cause of intramammary infection and mastitis in dairy cattle. Un... more Streptococcus uberis is a common cause of intramammary infection and mastitis in dairy cattle. Unlike other mammary pathogens, S. uberis evades detection by mammary epithelial cells, and the host–pathogen interactions during early colonisation are poorly understood. Intramammary challenge of dairy cows with S. uberis (strain 0140J) or isogenic mutants lacking the surface-anchored serine protease, SUB1154, demonstrated that virulence was dependent on the presence and correct location of this protein. Unlike the wild-type strain, the mutant lacking SUB1154 failed to elicit IL-1β from ex vivo CD14+ cells obtained from milk (bovine mammary macrophages, BMM), but this response was reinstated by complementation with recombinant SUB1154; the protein in isolation elicited no response. Production of IL-1β was ablated in the presence of various inhibitors, indicating dependency on internalisation and activation of NLRP3 and caspase-1, consistent with inflammasome activation. Similar transcrip...

Frontiers in Veterinary Science, 2017

Within the ruminant system, several possibilities exist to generate dendritic cells migrating out... more Within the ruminant system, several possibilities exist to generate dendritic cells migrating out from the tissue into the regional draining lymph nodes as afferent lymph dendritic cells (ALDCs). Here, we analyzed toll-like receptor (TLR) 1-10 mRNA expression by using quantitative real-time PCR in highly purified subsets of bovine ALDC. As TLR expression may be influenced by pathogens or vaccines and their adjuvant, it is necessary to understand what TLRs are expressed in a steady-state system to elucidate specific differences and to potentially optimize targeted vaccines. In this study, we have assessed the TLR expression profiles of the four main bovine ALDC subsets [cDC1 and cDC2 (subsets 2-4)]. We demonstrate differences in TLR expression between the four subsets that may reflect the ability of these cells to respond to different pathogens or to respond to adjuvants.

Reproduction Abstracts, 2016

European Journal of Clinical Microbiology Infectious Diseases, Mar 1, 1994

A multiply resistant serotype 23F pneumococcus was cultured from a 3-year-old child with otitis m... more A multiply resistant serotype 23F pneumococcus was cultured from a 3-year-old child with otitis media and five carriers at the child&amp;#39;s day-care centre in South Africa. Attempts to eradicate carriage with mupirocin failed. The strains were identical to the Spanish clone of multiply resistant pneumococci by serotype, antimicrobial susceptibility pattern, restriction analysis of the penicillin-binding protein 1A, 2B and 2X genes and by multilocus enzyme electrophoresis. The data suggest that this clone has acquired erythromycin resistance. A possible link between the index case and residence of a family member in Spain was found.

Veterinary Research, Mar 14, 2012

The Journal of Immunology, Apr 1, 2007

BMC genomics, Jan 23, 2015

Streptococcus uberis, a Gram-positive, catalase-negative member of the family Streptococcaceae is... more Streptococcus uberis, a Gram-positive, catalase-negative member of the family Streptococcaceae is an important environmental pathogen responsible for a significant proportion of subclinical and clinical bovine intramammary infections. Currently, the genome of only a single reference strain (0140J) has been described. Here we present a comparative analysis of complete draft genome sequences of an additional twelve S. uberis strains. Pan and core genome analysis revealed the core genome common to all strains to be 1,550 genes in 1,509 orthologous clusters, complemented by 115-246 accessory genes present in one or more S. uberis strains but absent in the reference strain 0140J. Most of the previously predicted virulent genes were present in the core genome of all 13 strains but gene gain/loss was observed between the isolates in CDS associated with clustered regularly interspaced short palindromic repeats (CRISPRs), prophage and bacteriocin production. Experimental challenge experiment...

Vaccine, Jan 17, 2006

Mycobacterium bovis is the causative agent of bovine tuberculosis (TB) and of a proportion of hum... more Mycobacterium bovis is the causative agent of bovine tuberculosis (TB) and of a proportion of human TB. Protection against TB requires Th1 responses and worsening of disease is associated with Th2 responses. To help clarify the nature of the response to mycobacteria, the responses from M. bovis-BCG vaccinated cattle boosted with live mycobacteria (BCG), bacterial soluble antigens (PPD) or PBS were evaluated. The results indicated that macrophages may be the major cell population ingesting and presenting mycobacteria in BCG boosted animals, while B-cells seem able to ingest and present PPD to T-cells in PPD boosted animals.

Veterinary Immunology and Immunopathology, 2012

Chemokines play a key role in initiating the innate and subsequently adaptive immune response by ... more Chemokines play a key role in initiating the innate and subsequently adaptive immune response by recruiting immune cells to the site of an infection. Monocytes/macrophages (MØ) are part of the first line of defence against invading pathogens, and have been shown to release a variety of chemokines in response to infection. Here, we reveal the early transcriptional response of MØ to infection with cytopathogenic (cp) and non-cytopathogenic (ncp) bovine viral diarrhoea strains (BVDV). We demonstrate up-regulation of several key chemokines of the CCL and CXCL families in MØ exposed to cpBVDV, but not ncpBVDV. In contrast, infection of MØ with ncpBVDV led to down-regulation of chemokine mRNA expression compared to uninfected cells. Data suggest that ncpBVDV can shut down production of several key chemokines that play crucial roles in the immune response to infection. This study helps to further our understanding of the pathogenesis of BVDV infection, highlighting biotype-specific cellular responses.

The Veterinary record, Jan 22, 2004

Microbial drug resistance (Larchmont, N.Y.), 1995

Penicillin-resistant pneumococci have been reported with increasing frequency in recent years. Is... more Penicillin-resistant pneumococci have been reported with increasing frequency in recent years. Isolates with high-level resistance are now found in many countries, and in some countries they constitute a substantial proportion of all isolates. A worrying development is the recent emergence of pneumococci with high-level resistance to third-generation cephalosporins. Resistance to beta-lactam antibiotics in pneumococci is due entirely to the development of altered forms of the high-molecular-weight penicillin-binding proteins (PBPs) that have decreased affinity for the antibiotics. High-level resistance to third-generation cephalosporins has occurred by the development of altered forms of PBP1a and 2x, whereas high-level penicillin resistance additionally requires alterations of PBP2b. Altered PBPs are encoded by mosaic genes that have emerged by recombinational events between the pbp genes of pneumococci and their homologs in closely related streptococcal species. Horizontal gene tr...

Veterinary Immunology and Immunopathology, 2009

animals we have also purpose bred MHC homozygous animals covering each of the four haplotypes. In... more animals we have also purpose bred MHC homozygous animals covering each of the four haplotypes. In addition to providing a valuable cellular resource for analysis of T cell responses, these homozygous animals also allow the unambiguous molecular genetic characterisation of the four target MHC haplotypes. Here we describe the characterization of the transcribed MHC class I and class II genes carried by these distinct haplotypes. This provides substantial new information on allelic and haplotype diversity in sheep. The MHC defined flock is available for collaborative studies of T cell responses to infectious livestock pathogens and will be valuable tools for subunit vaccine development and comparative studies of MHC diversity and evolution.

BMJ (Clinical research ed.), Jan 13, 2014

A randomised controlled trial that remained unpublished for 20 years casts doubt on the survival ... more A randomised controlled trial that remained unpublished for 20 years casts doubt on the survival benefit of further surgery after curative resection of colorectal cancer. Tom Treasure and colleagues tell the story of the first trial restored under the restoring invisible and abandoned trials initiative and discuss what it means today Tom Treasure professor 1 , Kathryn Monson researcher 2 , Francesca Fiorentino research fellow 3 ,

Frontiers in Immunology, 2013

in the most appropriate host, to examine the host-pathogen interactions that occur in outbred pop... more in the most appropriate host, to examine the host-pathogen interactions that occur in outbred populations. A fundamental point in the development of new and improved intervention strategies is the understanding of host differences in the innate immune response, which primes the subsequent adaptive immune response. Although the innate immune system has been largely conserved during evolution, marked variations and diversity exist between different mammalian species within Pattern-Recognition-Receptor (PRR) structure (Jungi et al., 2011). These differences are based on evolutionary pressure within the innate immune system, potentially reflecting the specific threats encountered by each species (Zhang et al., 2010). This selective pressure appears to be absent in the available murine sequences (Werling et al., 2009). The similarity between human and farm animal PRR (Jungi et al., 2011) is further supported by their similar response to ligands (Kapetanovic et al., 2012), in contrast to murine PRR (Hajjar et al., 2002; Grabiec et al., 2004; Farhat et al., 2010). Since recognition by PRR is associated with adaptive immunity by providing optimal immunostimulation, learning more about these key molecules in farm animals might inform us about their adjuvant effect in vaccines for use in these animals as well as humans. Given the size and blood volumes of farm animals, there are also greater opportunities to repeatedly access to different cell types-an asset which would facilitate the assessment of cell specific effects of such immunomodulatory agents on autologous cells (Hein and Griebel, 2003). Farm animal models do have their disadvantages such as dedicated housing, biosecurity, and the confinement of infected animals. However, it is misleading to rely on murine

Frontiers in Microbiology, 2014

Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of l... more Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of livestock-associated methicillin-resistant S. aureus infections in Europe and North America. This strain is characterized by high promiscuity in terms of host-species and also lacks several traditional S. aureus virulence factors. This does not, however, explain the apparent ease with which it crosses species-barriers. Recently, TIR-domain containing proteins (Tcps) which inhibit the innate immune response were identified in some Gramnegative bacteria. Here we report the presence of two proteins, S. aureus TIR-like Protein 1 (SaTlp1) and S. aureus TIR-like Protein 2 (SaTlp2), expressed by ST398 which contain domain of unknown function 1863 (DUF1863), similar to the Toll/IL-1 receptor (TIR) domain. In contrast to the Tcps in Gram-negative bacteria, our data suggest that SaTlp1 and SaTlp2 increase activation of the transcription factor NF-κB as well as downstream pro-inflammatory cytokines and immune effectors. To assess the role of both proteins as potential virulence factors knockout mutants were created. These showed a slightly enhanced survival rate in a murine infectious model compared to the wild-type strain at one dose. Our data suggest that both proteins may act as factors contributing to the enhanced ability of ST398 to cross species-barriers.

Journal of Leukocyte Biology, 2008

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) C-type lectin is almost exclu- sive... more Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) C-type lectin is almost exclu- sively expressed at the cell surface of DC. In addition to its normal function facilitating contact of DC with T cells, DC-SIGN has been shown to bind a variety of pathogens, including Mycobacterium bovis, and HIV-1 envelope protein gp120. In this study, we identified the bovine ortholog of the human