Biology subjects

Ollivier, V.

Publications and source records attributed to Ollivier, V..

3 recordsLinked to original sources

bioRxiv2025

Neutrophil extracellular traps block endogenous and intravenous thrombolysis-induced fibrinolysis in large vessel occlusion acute ischemic stroke

BackgroundIntravenous thrombolysis (IVT) failure in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is frequent but its causes remain elusive. Several non-exclusive mechanisms have been proposed to explain IVT failure, including failed delivery of tPA and inhibition of its activity. We investigated whether biologically relevant intrathrombus concentrations of t-PA were achieved in failed IVT in patients with LVO AIS, and whether neutrophil extracellular traps (NETs) contributed to IVT failure. MethodsIn this cohort study, a total of 205 thrombi from AIS patients with LVO were analyzed. 83 of these thrombi were compared for tPA content and 53 for their susceptibility to ex vivo thrombolysis according to IVT status. An additional subset of 69 AIS thrombi was used to decipher if and how NETs interfere with intrathrombus fibrinolysis. ResultsAIS thrombi from IVT patients contained more tPA than those from no-IVT patients (0.209 vs 0.093 {micro}g/mg of thrombus, p<0.0001). Plasminogen and tPA in AIS thrombi were found in association with fibrin and NETs. The ability of NETs to bind tPA and plasminogen, titrating them away from fibrin, was confirmed in a microfluidic model of thrombosis. While ex vivo addition of plasminogen did not cause lysis of either no-IVT or IVT thrombi, combining plasminogen with DNase 1 helped translate the increased tPA content of IVT thrombi into increased thrombolysis. We further show that DNase 1 enables tPA- and plasmin-mediated thrombolysis by eliminating fibrinolysis inhibitors from AIS thrombi. ConclusionsThese results indicate that intrathrombus tPA concentrations reached in failed IVT bear a therapeutic potential that is however impaired by NETs, which favor intrathrombus retention of fibrinolysis inhibitors and compete with fibrin for tPA and plasminogen binding. Our results stress the interest of DNase 1 to enhance the efficacy of current IVT tPA regimens. Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIIntravenous thrombolysis increases thrombus tPA content even when it fails to cause arterial recanalization in acute ischemic stroke C_LIO_LIThe fibrinolytic activity of intravenously-administered tPA is blocked by neutrophil extracellular traps in acute ischemic stroke thrombi C_LIO_LINeutrophil extracellular traps participate in thrombolysis resistance by retaining fibrinolysis inhibitors and titrating tPA and plasminogen away from fibrin in acute ischemic stroke thrombi C_LIO_LIDNase 1 can convert increased tPA content into increased fibrinolysis by eliminating NETs-associated fibrinolysis inhibitors in acute ischemic stroke thrombi C_LI 2) What are the clinical implications?O_LIDespite therapeutic failure, biologically significant intrathrombus tPA concentrations are achieved following intravenous thrombolysis at current tPA regimens C_LIO_LISequential administration of DNase 1 prior to intravenous thrombolysis could clear the way for tPA and potentiate its fibrinolytic activity for improved arterial recanalization efficacy C_LI

pathology↗

bioRxiv2025

Effects of host sex, age and behaviour on co-infection patterns in a wild ungulate

Recent zoonotic disease emergences reveal the importance of studying wildlife parasite communities. As wild hosts frequently harbour diverse parasite species, understanding the drivers of multiple infection patterns in free-ranging hosts is critical for elucidating the ecological and epidemiological dynamics of parasite communities. In this study, we analysed co-infection patterns in European roe deer (Capreolus capreolus) inhabiting a fragmented rural landscape in southwestern France. Using data from 130 GPS-tracked roe deer, we examined the influence of proximity to livestock, host activity levels, age, sex, and between-parasite interactions on the presence of 11 parasitic taxa. Hierarchical modelling of species communities (HMSC) revealed that proximity to livestock significantly increased the likelihood of infection with orofecally transmitted parasites (Toxoplasma gondii, gastrointestinal parasites). Sex and age were other key predictors, with males and juveniles exhibiting a higher frequency of parasite presence, likely influenced by hormonal and immune system differences. Activity levels showed distinct age-related effects, with higher activity levels being positively associated with increased parasite prevalence in yearlings, but not in adults. In contrast, parasite association patterns within individual hosts were weak, suggesting minimal interactions between parasite species. Our findings highlight the interplay between exposure and susceptibility in shaping co-infection patterns and underscore the value of hierarchical modelling approaches in multi-parasite systems. Key FindingsO_LIParasite communities, studied in 130 GPS monitored roe deer, revealed frequent co-infection. C_LIO_LIProximity to livestock increased the risk of infection by parasite taxa shared with domestic animals. C_LIO_LIFor several parasitic taxa, males and younger roe deer had a higher probability of infection. C_LIO_LIThe effect of host activity on parasite infection was dependent on roe deer age. C_LIO_LIOnly slight between-parasite interactions were detected within individual hosts. C_LI

ecology↗

bioRxiv2025

Spatial pattern of serology against Borrelia and tick-borne encephalitis virus in roe deer (Capreolus capreolus), Northern France, 2019-2022

BackgroundLyme borreliosis and tick-borne encephalitis (TBE) are tick-borne zoonoses of public health importance, transmitted in Western Europe by the same tick vector Ixodes ricinus. Roe deer (Capreolus capreolus) is a widespread feeding host for I. ricinus stages. Here, we explored the spatial extent of both pathogens in the wild in Northern France by assessing serological status in roe deer. MethodsWe collected 3,147 blood samples (2019-2022), and searched antibodies against both pathogens using ELISA tests. We fitted logistic models to investigate exposure to both or either pathogens, and explored spatial patterns using Kulldorf clustering scan tests. ResultsThe overall ELISA IgG prevalence was 23.24% (95%CI [21.77-34.72]) for Borrelia and 8.64% (95%CI [7.45-9.86]) for TBEV. The median Borrelia seroprevalence varied from 4% to 42% between departments, with two high-risk clusters of exposure identified. TBEV seroprevalence did not show any spatial pattern, and positives by seroneutralisation tests were reported in eight departments. DiscussionOur findings suggest the presence of both pathogens over large areas. Wider spatial sampling including areas at lower risk and improved serological methods would be beneficial to further validate those estimates.

ecology↗