Biology subjects

Glenn, L.

Publications and source records attributed to Glenn, L..

3 recordsLinked to original sources

bioRxiv2026

A faster incubation explains Usutu leading West Nile in temperate Europe

Usutu virus (USUV) is a mosquito-borne flavivirus that has recently expanded northwards in Europe and become endemic in the UK. USUV emergence often precedes the closely related West Nile virus (WNV), potentially reflecting differences in epidemiological parameters. One key parameter is the extrinsic incubation period (EIP), the time taken for a mosquito to become infectious after a blood meal. Here we present the first quantitative estimate of the temperature dependent EIP for USUV in the vector Culex pipiens molestus. We were able to quantify the shortening of the USUV EIP from 68.06 days (95% CrI: 38.62 to 141.04) at 17 {degrees}C to 12.35 days (95% CrI: 8.10 to 17.09) at 25{degrees}C. This was achieved by re-analysing laboratory data with a bespoke Bayesian model that accounted for important features of the experimental design. Under UK summer temperatures, the median EIP of USUV is 37.75% (95% CrI: 3.38 to 55.68) shorter than that of WNV, and the potential transmission season of USUV is both longer and geographically more extensive. Under RCP8.5 climate projections, WNV transmission suitability could match or exceed current USUV levels between 2055 and 2065, highlighting the future threat to the UK from emerging mosquito borne pathogens. Our findings support USUV as a precursor for WNV in Europe and provide a robust characterisation of a key epidemiological parameter of USUV, enabling accurate modelling of its transmission dynamics.

ecology↗

bioRxiv2024

Development of antisense tools to study Bodo saltans and its intracellular symbiont

Obligate symbioses are common in nature and present a particular challenge for functional genetic analysis. In many cases, the host is a non-model species with poor tools for genetic manipulation and the symbiont cannot be cultured or its gene expression manipulated to investigate function. Here we investigated the potential for using antisense inhibition to analyse host and symbiont gene function within an obligate aquatic symbiosis. We focused on the kinetoplastid host Bodo saltans and its bacterial symbiont, Candidatus Bodocaedibacter vickermanii, a member of Rickettsiales. We conclude that antisense inhibition is not feasible in the B. saltans and its symbiont, as the holobiont feeds on the antisense molecules - and increases in numbers - upon treatment with the antisense construct. Although our approach has proven unsuccessful, we have developed an array of protocols which can be used to study the biology of this microeukaryote and its microbial associates.

molecular biology↗

bioRxiv2021

12-Lipoxygenase Governs the Innate Immune Pathogenesis of Islet Inflammation and Autoimmune Diabetes

Macrophages and related myeloid cells are innate immune cells that participate in the early islet inflammation of type 1 diabetes (T1D). The inflammatory signals and antigen presentation by these cells may be inducers of the adaptive immune response that is the hallmark of T1D. The enzyme 12-lipoxygenase (12-LOX) catalyzes the formation of pro-inflammatory eicosanoids from membrane-derived phospholipids, but its role and mechanisms in the pathogenesis of islet inflammation have not been elucidated. Leveraging a model of T1D-like islet inflammation in zebrafish, we show here that macrophages contribute significantly to the loss of {beta}-cells and the subsequent development of hyperglycemia. Depletion or inhibition of 12-LOX in this model resulted in significantly reduced macrophage infiltration into islets with preservation of {beta}-cell mass. In mice, we deleted the gene encoding 12-LOX (Alox15) in the myeloid lineage in the non-obese diabetic (NOD) model of T1D. Myeloid cell-specific Alox15 knockout NOD mice demonstrated reduced insulitis and T-cell responses, preserved {beta} cell mass, and almost complete protection from the development of T1D. A critical effect of 12-LOX depletion appeared secondary to a defect in myeloid cell migration, a function required for immune surveillance and tissue injury responses. This effect on migration appeared to be secondary to the loss of the chemokine receptor CXCR3. Transgenic expression of the gene encoding CXCR3 rescued the migrator defect in zebrafish 12-LOX morphants. Taken together, our results reveal a formative role for innate immune myeloid cells in the early pathogenesis of T1D and identify 12-LOX as a necessary enzyme to promote their pro-diabetogenic phenotype in the context of autoimmunity.

immunology↗