ORCID Profile
0000-0003-2962-8726
Current Organisation
University of Southampton
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Publisher: American Society for Microbiology
Date: 12-2003
DOI: 10.1128/IAI.71.12.6830-6834.2003
Abstract: Inbred strains of mice infected with Leishmania major have been classified as genetically resistant or susceptible on the basis of their ability to cure their lesions, the parasite burden in the draining lymph nodes, and their type of T helper cell immune responses to the parasite. Using the intradermal infection at the base of the tail and the ear pinna, we compared for the first time the above-mentioned parameters in six strains of mice infected with metacyclic promastigotes, and we show that the severity of disease depends greatly on the site of infection. Although the well-documented pattern of disease susceptibility of BALB/c and C57BL/6 mice described for the footpad and base-of-the-tail models of leishmaniasis were confirmed, C3H/HeN and DBA/2 mice, which are intermediate and susceptible, respectively, in the tail and other models, were resistant to ear infection. Moreover, in the CBA/H, C3H/HeN, C57BL/6J, and DBA/2 mouse strains, there was little correlation between the pattern of cytokines produced and the disease phenotype observed at the ear and tail sites. We conclude that the definition of susceptibility and the immune mechanisms leading to susceptibility or resistance to infection may differ substantially depending on the route of infection.
Publisher: American Society for Microbiology
Date: 03-2018
DOI: 10.1128/IAI.00812-17
Abstract: Mycoplasmas are bacterial pathogens of a range of animals, including humans, and are a common cause of respiratory disease. However, the host genetic factors that affect resistance to infection or regulate the resulting pulmonary inflammation are not well defined. We and others have previously demonstrated that nonobese diabetic (NOD) mice can be used to investigate disease loci that affect bacterial infection and autoimmune diabetes. Here we show that NOD mice are more susceptible than C57BL/6 (B6) mice to infection with Mycoplasma pulmonis , a natural model of pulmonary mycoplasmosis. The lungs of infected NOD mice had higher loads of M. pulmonis and more severe inflammatory lesions. Moreover, congenic NOD mice that harbored different B6-derived chromosomal intervals enabled identification and localization of a new mycoplasmosis locus, termed Mpr2 , on chromosome 13. These congenic NOD mice demonstrated that the B6 allele for Mpr2 reduced the severity of pulmonary inflammation caused by infection with M. pulmonis and that this was associated with altered cytokine and chemokine concentrations in the infected lungs. Mpr2 also colocalizes to the same genomic interval as Listr2 and Idd14 , genetic loci linked to listeriosis resistance and autoimmune diabetes susceptibility, respectively, suggesting that allelic variation within these loci may affect the development of both infectious and autoimmune disease.
Publisher: Wiley
Date: 22-05-2023
DOI: 10.1111/BTP.13231
Abstract: Here, we investigate Mid‐ to Late‐Holocene vegetation changes in low‐lying coastal areas in Tonga and how changing sea levels and recurrent volcanic eruptions have influenced vegetation dynamics on four islands of the Tongan archipelago (South Pacific). To investigate past vegetation and environmental change at Ngofe Marsh (‘Uta Vava’u), we examined palynomorphs (pollen and spores), charcoal (fire), and sediment characteristics (volcanic activity) from a 6.7‐m‐long sediment core. Radiocarbon dating indicated the sediments were deposited over the last 7700 years. We integrated the Ngofe Marsh data with similar previously published data from Avai’o’vuna Sw on Pangaimotu Island, Lotofoa Sw on Foa Island, and Finemui Sw on Ha’afeva Island. Plant taxa were categorized as littoral, mangrove, rainforest, successional/ disturbance, and wetland groups, and linear models were used to examine relationships between vegetation, relative sea level change, and volcanic eruptions (tephra). We found that relative sea level change has impacted vegetation on three of the four islands investigated. Volcanic eruptions were not identified as a driver of vegetation change. Rainforest decline does not appear to be driven by sea level changes or volcanic eruptions. From all sites analyzed, vegetation at Finemui Sw was most sensitive to changes in relative sea level. While vegetation on low‐lying Pacific islands is sensitive to changing sea levels, island characteristics, such as area and elevation, are also likely to be important factors that mediate specific island responses to drivers of change.
Publisher: Springer Science and Business Media LLC
Date: 11-12-2004
Publisher: Proceedings of the National Academy of Sciences
Date: 13-10-2005
Abstract: Chronic microbial infections are associated with fibrotic and inflammatory reactions known as granulomas showing similarities to wound-healing and tissue repair processes. We have previously mapped three leishmaniasis susceptibility loci, designated lmr1 , - 2 , and - 3 , which exert their effect independently of T cell immune responses. Here, we show that the wound repair response is critically important for the rapid cure in murine cutaneous leishmaniasis caused by Leishmania major . Mice congenic for leishmaniasis resistance loci, which cured their lesions more rapidly than their susceptible parents, also expressed differentially genes involved in tissue repair, laid down more ordered collagen fibers, and healed punch biopsy wounds more rapidly. Fibroblast monolayers from these mice repaired in vitro wounds faster, and this process was accelerated by supernatants from infected macrophages. Because these effects are independent of T cell-mediated immunity, we conclude that the rate of wound healing is likely to be an important component of innate immunity involved in resistance to cutaneous leishmaniasis.
Publisher: Wiley
Date: 23-03-2023
DOI: 10.1111/ELE.14196
Abstract: Human‐mediated changes in island vegetation are, among others, largely caused by the introduction and establishment of non‐native species. However, data on past changes in non‐native plant species abundance that predate historical documentation and censuses are scarce. Islands are among the few places where we can track human arrival in natural systems allowing us to reveal changes in vegetation dynamics with the arrival of non‐native species. We matched fossil pollen data with botanical status information (native, non‐native), and quantified the timing, trajectories and magnitude of non‐native plant vegetational change on 29 islands over the past 5000 years. We recorded a proportional increase in pollen of non‐native plant taxa within the last 1000 years. In idual island trajectories are context‐dependent and linked to island settlement histories. Our data show that non‐native plant introductions have a longer and more dynamic history than is generally recognized, with critical implications for bio ersity baselines and invasion biology.
Publisher: Wiley
Date: 23-07-2013
DOI: 10.1002/DVG.22409
Abstract: Pax6 encodes a transcription factor with key roles in the development of the pancreas, central nervous system, and eye. Gene expression is orchestrated by several alternative promoters and enhancer elements that are distributed over several hundred kilobases. Here, we describe a reciprocal translocation, called 1Gso, which disrupts the integrity of transcripts arising from the 5'-most promoter, P0, and separates downstream promoters from enhancers active in pancreas and eye. Despite this fact, 1Gso animals exhibit none of the dominant Pax6 phenotypes, and the translocation complements recessive brain and craniofacial phenotypes. However, 1Gso fails to complement Pax6 recessive effects in lacrimal gland, conjunctiva, lens, and pancreas. The 1Gso animals also express a corneal phenotype that is related to but distinct from that expressed by Pax6 null mutants, and an abnormal density and organization of retinal ganglion cell axons these phenotypes may be related to a modest upregulation of Pax6 expression from downstream promoters that we observed during development. Our investigation maps the activities of Pax6 alternative promoters including a novel one in developing tissues, confirms the phenotypic consequences of upstream enhancer disruption, and limits the likely effects of the P0 transcript null mutation to recessive abnormalities in the pancreas and specific structures of the eye.
Publisher: Elsevier
Date: 2005
Publisher: Springer Science and Business Media LLC
Date: 07-06-2014
DOI: 10.1007/S00251-014-0782-5
Abstract: The nonobese diabetic (NOD) mouse strain serves as a genomic standard for assessing how allelic variation for insulin-dependent diabetes (Idd) loci affects the development of autoimmune diabetes. We previously demonstrated that C57BL/6 (B6) mice harbor a more diabetogenic allele than NOD mice for the Idd14 locus when introduced onto the NOD genetic background. New congenic NOD mouse strains, harboring smaller B6-derived intervals on chromosome 13, now localize Idd14 to an ~18-Mb interval and reveal a new locus, Idd31. Notably, the B6 allele for Idd31 confers protection against diabetes, but only in the absence of the diabetogenic B6 allele for Idd14, indicating genetic epistasis between these two loci. Moreover, congenic mice that are more susceptible to diabetes are more resistant to Listeria monocytogenes infection. This result co-localizes Idd14 and Listr2, a resistance locus for listeriosis, to the same genomic interval and indicates that congenic NOD mice may also be useful for localizing resistance loci for infectious disease.
Publisher: Oxford University Press (OUP)
Date: 04-10-2015
Publisher: Cold Spring Harbor Laboratory
Date: 12-06-2002
DOI: 10.1101/GR.GR-1578R
Publisher: American Society for Microbiology
Date: 06-2010
DOI: 10.1128/IAI.00126-10
Abstract: Genetic linkage studies of the host response to Leishmania major , the causative agent of cutaneous leishmaniasis, have identified significant genetic complexity in humans and mice. In the mouse model, multiple loci have been implicated in susceptibility to infection, but to date, the genes underlying these loci have not been identified. We now describe the contribution of a novel candidate gene, Fli1 , to both L. major resistance and enhanced wound healing. We have previously mapped the L. major response locus, lmr2 , to proximal chromosome 9 in a genetic cross between the resistant C57BL/6 strain and the susceptible BALB/c strain. We now show that the presence of the resistant C57BL/6 lmr2 allele in susceptible BALB/c mice confers an enhanced L. major resistance and wound healing phenotype. Fine mapping of the lmr2 locus permitted the localization of the lmr2 quantitative trait locus to a 5-Mb interval comprising 21 genes, of which microarray analysis was able to identify differential expression in 1 gene— Fli1 . Analysis of Fli1 expression in wounded and L. major -infected skin and naïve and infected lymph nodes validated the importance of Fli1 in lesion resolution and wound healing and identified 3 polymorphisms in the Fli1 promoter, among which a GA repeat element may be the important contributor.
Publisher: Oxford University Press (OUP)
Date: 07-2008
DOI: 10.1093/JNCIMONOGRAPHS/LGN008
Abstract: Translocations have provided invaluable tools for identifying both cancer-linked genes and loci associated with heritable human diseases, but heritable human translocations are rare and few mouse models exist. Here we report progress on analysis of a collection of heritable translocations generated by treatment of mice with specific chemicals or radiation during late spermatogenic stages. The translocation mutants exhibit a range of visible phenotypes reflecting the disruption of coding sequences or the separation of genes from essential regulatory elements. The breakpoints of both radiation-induced and chemically induced mutations in these mice are remarkably clean, with very short deletions, duplications, or inversions in some cases, and ligation mediated by microhomology, suggesting nonhomologous end joining as the major path of repair. These mutations provide new tools for the discovery of novel genes and regulatory elements linked to human developmental disorders and new clues to the molecular basis of human genetic disease.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2004
Publisher: American Association for the Advancement of Science (AAAS)
Date: 12-02-2016
Abstract: One of the enduring mysteries of autoimmunity is the identity of the specific proteins targeted by autoimmune T cells. Delong et al. used mass spectrometry to elucidate the peptide targets of autoimmune T cells isolated from a mouse model of type 1 diabetes. T cells targeted hybrid peptides formed by the covalent linking of a peptide derived from pro-insulin to other peptides derived from proteins found in pancreatic beta cells. T cells isolated from the pancreatic islets of two in iduals with type 1 diabetes also recognized such hybrid peptides, suggesting that they may play an important role in driving disease. Science , this issue p. 711
Publisher: Cold Spring Harbor Laboratory
Date: 04-11-2010
Abstract: More than 25 loci have been linked to type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse, but identification of the underlying genes remains challenging. We describe here the positional cloning of a T1D susceptibility locus, Idd11 , located on mouse chromosome 4. Sequence analysis of a series of congenic NOD mouse strains over a critical 6.9-kb interval in these mice and in 25 inbred strains identified several haplotypes, including a unique NOD haplotype, associated with varying levels of T1D susceptibility. Haplotype ersity within this interval between congenic NOD mouse strains was due to a recombination hotspot that generated four crossover breakpoints, including one with a complex conversion tract. The Idd11 haplotype and recombination hotspot are located within a predicted gene of unknown function, which exhibits decreased expression in relevant tissues of NOD mice. Notably, it was the recombination hotspot that aided our mapping of Idd11 and confirms that recombination hotspots can create genetic variation affecting a common polygenic disease. This finding has implications for human genetic association studies, which may be affected by the approximately 33,000 estimated hotspots in the genome.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.MOLIMM.2016.12.007
Abstract: During immune cell activation, serine-derived lipids such as phosphatidylserine and sphingolipids contribute to the formation of protein signaling complexes within the plasma membrane. Altering lipid composition in the cell membrane can subsequently affect immune cell function and the development of autoimmune disease. Serine incorporator 1 (SERINC1) is a putative carrier protein that facilitates synthesis of serine-derived lipids. To determine if SERINC1 has a role in immune cell function and the development of autoimmunity, we characterized a mouse strain in which a retroviral insertion abolishes expression of the Serinc1 transcript. Expression analyses indicated that the Serinc1 transcript is readily detectable and expressed at relatively high levels in wildtype macrophages and lymphocytes. The ablation of Serinc1 expression in these immune cells, however, did not significantly alter serine-derived lipid composition or affect macrophage function and lymphocyte proliferation. Analyses of Serinc1-deficient mice also indicated that systemic ablation of Serinc1 expression did not affect viability, fertility or autoimmune disease susceptibility. These results suggest that Serinc1 is dispensable for certain immune cell functions and does not contribute to previously reported links between lipid composition in immune cells and autoimmunity.
Publisher: Springer Science and Business Media LLC
Date: 06-11-2018
DOI: 10.1007/S00125-018-4760-6
Abstract: Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of pancreatic insulin-producing beta cells. The epitopes recognised by pathogenic T cells in human type 1 diabetes are poorly defined however, a growing body of evidence suggests that T cell responses against neoepitopes contribute to beta cell destruction in type 1 diabetes. Neoepitopes are formed when self-proteins undergo post-translational modification to create a new epitope that is recognised by T- or B cells. Here we review the role of human T cell responses against neoepitopes in the immune pathogenesis of type 1 diabetes. Specifically, we review the different approaches to identifying neoepitopes relevant to human type 1 diabetes and outline several advances in this field that have occurred over the past few years. We also discuss the application of neoepitopes to the development of antigen-specific therapies for type 1 diabetes and the unresolved challenges that need to be overcome before the full repertoire of neoepitopes recognised by pathogenic human T cells in type 1 diabetes can be determined. This information may then be used to develop antigen-specific therapies for type 1 diabetes and assays to monitor changes in pathogenic, beta cell-specific T cell responses.
Publisher: Frontiers Media SA
Date: 23-02-2023
DOI: 10.3389/FEVO.2023.1087577
Abstract: Islands of the Southwest Pacific are exposed to geologic and climate-related disturbances that occur on a range of timescales and which probably affect, to varying degrees, their terrestrial ecosystems. Over the past ∼1100 years we know of two major events in the region: the Kuwae eruption which is thought to have occurred ∼500 cal. years BP and a shift to drier conditions which began ∼1100 cal. years BP. We investigated terrestrial and lacustrine ecosystem responses to these events and also to a changing fire regime, likely human-caused, using a multi-proxy (C/N, charcoal, chironomids, pollen, and tephra) record from Lake Emaotul, Efate, Vanuatu. Tephra from the Kuwae eruption was found across a 6 cm layer which our age-depth model suggests was deposited 650–510 cal. years BP (95% confidence). Forest and chironomid community turnover increased during the wet-dry shift 1100–1000 cal. years BP subsequently, chironomid turnover rates decreased again within & years and vegetation had partially (but not fully) recovered after ∼80 years. Following Kuwae volcanic tephra deposition, vegetation turnover increased again, reflecting a reduction in small trees and shrubs and an increase in grasses. Subsequently, the forest vegetation did not regain its previous composition, whereas chironomid community composition remained fairly stable before and after tephra deposition. Within the last ∼90 years, enhanced local burning drove another increase in vegetation turnover. Terrestrial and freshwater ecosystems in Efate are sensitive to changes in hydroclimate, volcanism, and anthropogenic fires, although to different degrees while recent human impacts are often obvious, volcanic eruptions and climatic shifts have also structured Pacific-island ecosystems and will continue to do so.
Publisher: Public Library of Science (PLoS)
Date: 10-12-2019
Publisher: Elsevier BV
Date: 08-2014
Publisher: Proceedings of the National Academy of Sciences
Date: 10-2018
Abstract: Type 1 diabetes (T1D) is an incurable autoimmune disease caused by T cell-mediated destruction of insulin-producing beta cells. The beta-cell antigens recognized by human CD4 + T cells in T1D are poorly defined. Here, we show that C-peptide, derived from proinsulin, is recognized by CD4 + T cells from the blood of % of people with recent onset T1D. The majority of C-peptide–derived epitopes were recognized when presented by high-risk T1D HLA alleles. For some T cells, full-length C-peptide was a more potent stimulator than shorter peptides. Hence, our data suggests that full-length C-peptide may be uniquely antigenic in human T1D. C-peptide may be useful in assays to monitor changes in T cell autoimmunity and antigen-specific therapies for T1D.
Publisher: Springer Science and Business Media LLC
Date: 2005
DOI: 10.1007/S00335-004-2423-Z
Abstract: We describe two new mutations, 153Gso and 154Gso, associated with reciprocal translocations with a common breakpoint in mouse chromosome 6B3 (Mmu6B3). The translocations arose independently in offspring of male mice treated with chlorambucil and glycidamide, respectively. Homozygotes of both mutant stocks display a characteristic gait ataxia with 'foot-patting' behavior despite their ataxia the mutant animals are healthy, long-lived, and breed normally. Breeding experiments confirmed that 153Gso and 154Gso mutations are allelic, and both fail to complement a known mutation hotfoot (ho), a Mmu6 mutation involving the glutamate receptor gene, Grid2, that is associated with a virtually identical phenotype. Our studies demonstrate that the 153Gso and 154Gso mutations disrupt the Grid2 gene at sites located more than 100 kb apart in intron 6 and intron 4 of the gene, respectively. The occurrence of two independent translocations from a relatively small colony within the same locus supports data suggesting the hypermutability of the Grid2 locus and suggest that the gene's large size make it an especially likely target for mutations involving genetic rearrangement.
Publisher: Oxford University Press (OUP)
Date: 22-09-2004
DOI: 10.1093/HMG/DDH307
Publisher: The American Association of Immunologists
Date: 25-10-2023
Publisher: Wiley
Date: 07-12-2017
DOI: 10.1111/IMCB.1015
Abstract: For a long time, immunologists have believed that classical CD4
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Colleen Elso.