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Biology subjects

Mouton, L.

Publications and source records attributed to Mouton, L..

8 recordsLinked to original sources

Maternal immune activation imprints a regulatory T cell deficiency in offspring that drives an autism-like phenotype

Maternal immune activation (MIA) triggers an IL-17-driven autism spectrum disorder (ASD) in mouse and human offspring. While regulatory T cells (Tregs) regulate Th17 cells, their involvement in MIA and ASD pathogenesis is unknown. At the maternal level, we show that Treg stimulation suppresses interleukin-17 (IL-17) production and prevents ASD-like behaviors in offspring. At the offspring level, we show that MIA imprints a systemic and brain Treg deficiency, as evidenced by alterations in the methylome, transcriptome, and functional assays. This deficiency promotes brain inflammation, characterized by infiltration of IL-17-producing cells and neutrophils into the meninges and alterations in cortical brain structure. Stimulation of offspring Tregs with interleukin-2 reversed brain inflammation and cured established ASD-like behaviors. Thus, MIA-induced ASD is a neuroimmune disorder that can be reversed by immunomodulation. One sentence abstractMaternal immune activation during pregnancy imprints a Treg deficiency in offspring that perpetuates brain inflammation and an autism-like phenotype, which can be reversed by Treg stimulation.

immunology↗

Cerebral Venous Blood Flow Regulates Brain Fluid Clearance via Dural Lymphatics

The vascular system regulates brain clearance through arterial blood flow and lymphatic drainage of cerebrospinal fluid (CSF). Idiopathic intracranial hypertension (IIH), characterized by elevated intracranial pressure and dural venous sinus stenoses, can be treated by restoring venous blood flow via venous stenting, suggesting a role for venous blood flow in brain fluid clearance. Using magnetic resonance imaging (MRI) in IIH patients and healthy controls, we identified that dural venous stenoses in IIH were associated with impaired lymphatic drainage, perivenous fluid retention, and brain fluid accumulation. To investigate this further, we developed a mouse model with bilateral jugular vein ligation (JVL), which recapitulated key human findings, including intracranial hypertension, calvarial lymphatic regression, and brain swelling due to impaired clearance. To further dissect the respective roles of dural lymphatics and venous blood flow in brain clearance, we performed JVL in mice with dural lymphatic depletion. These mice exhibited spontaneous elevated intracranial pressure, but JVL did not further exacerbate this effect. Moreover, the synchronous restoration of brain clearance and dural lymphatics observed in mice after JVL was absent in lymphatic-deficient mice.Transcriptomic analyses revealed that lymphatic remodeling induced by JVL was driven by VEGF-C signaling between dural mesenchymal and lymphatic endothelial cells. These findings establish the dural venous sinuses as a critical platform where venous blood flow interacts with mesenchymal cells to preserve dural lymphatic integrity and function, essential for brain fluid clearance.

neuroscience↗

Longitudinal neuromelanin changes in prodromal and early Parkinson's disease in humans and rat model

Studies in animal models of Parkinsons disease (PD) suggested that the accumulation of the neuromelanin (NM), a pigment contained in nigral dopaminergic neurons, could trigger neurodegeneration above a pathogenic threshold. Here we investigated this hypothesis using NM-sensitive MRI in rodents and in patients with isolated rapid eye movement sleep disorders (iRBD) subjects, a prodromal phase of parkinsonism, and early PD. We first combined NM-sensitive MRI and histology to study NM accumulation and neurodegeneration in a humanized rat model of PD. NM-MRI signal changes were biphasic with an initial increase due to the accumulation of NM in dopaminergic neurons, followed signal decrease due to neurodegeneration. In healthy subjects and patients with iRBD, NM-MRI signal increased initially and then decreased similarly as in rodents after reaching a similar maximum signal intensity in both groups. In early PD and converted iRBD patients, NM-MRI signal drop was greater than in healthy individuals. Results in animals and humans show that NM-sensitive MRI is a marker of the intracellular NM accumulation up to a threshold then of neuronal degeneration beyond this threshold and agree with the hypothesis of a pathogenic threshold of NM triggering neurodegeneration.

neuroscience↗

Insect population dynamics under Wolbachia-induced cytoplasmic incompatibility: puzzle more than buzz in Drosophila suzukii

In theory, the introduction of individuals infected with an incompatible strain of Wolbachia pipientis into a recipient host population should result in the symbiont invasion and reproductive failures caused by cytoplasmic incompatibility (CI). Modelling studies combining Wolbachia invasion and host population dynamics show that these two processes could interact to cause a transient population decline and, in some conditions, extinction. However, these effects could be sensitive to density dependence, with the Allee effect increasing the probability of extinction, and competition reducing the demographic impact of CI. We tested these predictions with laboratory experiments in the fruit fly Drosophila suzukii and the transinfected Wolbachia strain wTei. Surprisingly, the introduction of wTei into D. suzukii populations at carrying capacity did not result in the expected wTei invasion and transient population decline. In parallel, we found no Allee effect but strong negative density dependence. From these results, we propose that competition interacts in an antagonistic way with Wolbachia-induced cytoplasmic incompatibility on insect population dynamics. If future models and data support this hypothesis, pest management strategies using Wolbachia-induced CI should target populations with negligible competition but a potential Allee effect, for instance at the beginning of the reproductive season.

ecology↗

Larval density in the invasive Drosophila suzukii: immediate and delayed effects on life-history traits

The immediate and delayed effects of density are key in determining population dynamics, since they can positively or negatively affect the fitness of individuals. These effects have great relevance for polyphagous insects for which immature stages develop within a single site of finite feeding resources. Drosophila suzukii is a crop pest that induces severe economic losses for agricultural production, however little is known about the effects of density on its life-history traits. In the present study, we (i) investigated the egg distribution resulting from females egg-laying strategy and (ii) tested the immediate and delayed effects of larval density on emergence rate, development time, sex ratio of offspring, fecundity and adult size (a range of 1 to 50 larvae was used). We showed that most of fruits contain several eggs and aggregate of eggs of high density can be found in some fruits. This high density has no immediate effects on the emergence rate, but has effect on larval developmental time. This trait was involved in a trade-off with adult life-history traits: the larval development was reduced as larval density increased, but smaller and less fertile adults were produced. Our results should help to better understand the population dynamics of this species and to develop more successful control programs.

ecology↗

Analyses of symbiotic bacterial communities in the plant pest Bemisia tabaci reveal high prevalence of Hemipteriphilus asiaticus on the African continent

AO_SCPLOWBSTRACTC_SCPLOWMicrobial symbionts are widespread in insects and some of them have been associated to adaptive changes. Primary symbionts (P-symbionts) have a nutritional role that allows their hosts to feed on unbalanced diets (plant sap, wood, blood). Most of them have undergone genome reduction, but their genomes still retain genes involved in pathways that are necessary to synthesize the nutrients that their hosts need. However, in some P-symbionts, essential pathways are incomplete and secondary symbionts (S-symbionts) are required to complete parts of their degenerated functions. The P-symbiont of the phloem sap-feeder Bemisia tabaci, Candidatus Portiera aleyrodidarium, lacks genes involved in the synthesis of vitamins, cofactors, and also of some essential amino-acids. Seven S-symbionts have been detected in the B. tabaci species complex. Phenotypic and genomic analyses have revealed various effects, from reproductive manipulation to fitness benefits, notably some of them have complementary metabolic capabilities to Candidatus Portiera aleyrodidarium, suggesting that their presence may be obligatory. In order to get the full picture of the symbiotic community of this pest, we investigated, through metabarcoding approaches, the symbiont content of individuals from Burkina Faso, a West African country where B. tabaci induces severe crop damage. While no new putative B. tabaci S-symbiont was identified, Candidatus Hemipteriphilus asiaticus, a symbiont only described in B. tabaci populations from Asia, was detected for the first time on this continent. Phylogenetic analyses however reveal that it is a different strain than the reference found in Asia. Specific diagnostic PCRs showed a high prevalence of these S-symbionts and especially of Candidatus Hemipteriphilus asiaticus in different genetic groups. These results suggest that Candidatus Hemipteriphilus asiaticus may affect the biology of B. tabaci and provide fitness advantage in some B. tabaci populations.

evolutionary biology↗

Insects and incest: field evidence for dangerous liaisons in a parasitoid wasp

O_LISib mating avoidance is a pervasive behaviour, which likely evolves in species that sare subject to inbreeding depression. Laboratory studies have provided elegant demonstrations, but small-scale bioassays often minimize the costs associated with mate finding and mate-choice and may for this reason produce spurious findings.\nC_LIO_LIWe inferred the mating behaviour of the parasitoid wasp Venturia canescens from the genetic analyses of natural populations. We used V. canescens as a model organism because in this species, laboratory experiments have shown that sib mating yields a 25% decrease in fertile offspring, and congruently, sib mating is partially avoided.\nC_LIO_LIOur study consisted in genotyping 86 wild-caught males, 155 wild-caught-females and their 226 daughters at eighteen microsatellite loci. With these data, we were able to reconstruct the genotype of females mate and estimate the relatedness of each mating pairs.\nC_LIO_LIWe found that the effective rate of sib mating does not differ from the probability that sibs encounter one another at random, which suggest a sib mating tolerance in this species. However, complementary lab experiments confirmed that kin discrimination exist in this species, with related pairs having a lower mating latency.\nC_LIO_LIThese results suggest that V. canescens tolerate sib mating in the field despite kin discrimination, and therefore call into question the common beliefs on inbreeding depression in species with single-locus complementary sex determination. This inbreeding tolerance also opens up the question of the maintenance of the kin discrimination in this species.\nC_LI

animal behavior and cognition↗

Modeling trophic dependencies and exchanges among insects’ bacterial symbionts in a host-simulated environment

Individual organisms are linked to their communities and ecosystems via metabolic activities. Metabolic exchanges and co-dependencies have long been suggested to have a pivotal role in determining community structure. Metabolic interactions with bacteria have been key drivers in the evolution of sap-feeding insects, enabling complementation of their deprived nutrition. The sap-feeding whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) harbors an obligatory symbiotic bacterium, as well as varying combinations of facultative symbionts. We took advantage of the well-defined bacterial community in B. tabaci as a case study for a comprehensive and systematic survey of metabolic interactions within the bacterial community and their associations with documented frequency of bacterial combinations. We first reconstructed the metabolic networks of five common B. tabaci symbionts (Portiera, Rickettsia, Hamiltonella, Cardinium and Wolbachia), and then used network analysis approaches to predict: (1) species-specific metabolic capacities in a simulated bacteriocyte-like environment; (2) metabolic capacities of the corresponding species combinations, and (3) dependencies of each species on different media components.\n\nThe automatic-based predictions for metabolic capacities of the symbionts in the host environment were in general agreement with previously reported genome analyses, each focused on the single-species level. The analysis suggested several previously un-reported routes for complementary interactions. Highly abundant symbiont combinations were found to have the potential to produce a diverse set of complementary metabolites, in comparison to un-detected combinations. No clear association was detected between metabolic codependencies and co-occurrence patterns. The findings indicate a potential key role for metabolic exchanges as key determinants shaping community structure in this system.

systems biology↗