Kinetic study of the antibody response during the blood meal of Ixodes ricinus: Implication on plasma cell maturation in vivo and for anti-Ixodes vaccination

peer reviewedAnti-tick vaccination could be an ideal solution to prevent pathogen transmission, but none is currently available against Ixodes ticks. Recently, we showed that adult Ixodes ricinus infestation on mice decreases the specific antibody production to BSA injected during infestation. Here, a kinetic study of seric levels of BSA-specific antibodies was performed to evaluate the B memory cell differentiation in Balb/c mice and the capacity of specific B memory cells to respond to BSA during infestation. We concluded that the tick blood meal inhibits or impairs the local differentiation of mature B cells into plasma cells, but does not alter the formation of memory B cell. Accordingly, this mechanism should not be an impediment to anti-Ixodes vaccination

Development of a quantitative surface-enhanced Raman scattering method for the analysis of dopamine in cell culture media

peer reviewedaudience: researcher, professiona

A simple and easy-to-implement SERS approach overcoming the nanoparticle stabilisation by serum proteins: application to dopamine and PC-12 cells

This lecture presents the different steps regarding the development of a label-free SERS analytical method that was able to overcome the nanoparticle stabilisation caused by serum proteins. It relied on the pre-aggregation of the SERS substrate, which was a suspension of gold nanoparticles. Furthermore, several applications of the developed methodology were presented: the quantification of dopamine in the culture medium of rat phaeochromocytoma PC-12 cells as well as the influence of calcium, potassium and dexamethasone on dopamine exocytosis from these cells

Interaction between dendritic cells and nerve fibres in lymphoid organs after oral scrapie exposure

peer reviewedIn transmissible spongiform encephalopathies (TSEs), the infectious agent, called PrPsc, an abnormal isoform of the cellular prion protein, accumulates and replicates in lymphoid organs before affecting the nervous system. To clarify the cellular requirements for the neuro-invasion of the scrapie agent from the lymphoid organs to the central nervous system, we have studied, by confocal microscopy, the innervations within Peyer's patches, mesenteric lymph nodes and the spleen of mice in physiological conditions and after oral exposure to prion. Contacts between nerve fibres and PrPsc-associated cells, dendritic cells (DCs) and follicular dendritic cells (FDCs), were evaluated in preclinical prion-infected mice. Using a double immunolabelling strategy, we demonstrated the lack of innervation of PrPsc-accumulating cells (FDCs). Contacts between nerve fibers and PrPsc-propagating cells (DCs) were detected in T-cell zones and cell-trafficking areas. This supports, for the first time, the possible implication of dendritic cells in the prion neuroinvasion process

Neutrophil Extracellular Traps (NET) Entrap and Kill Borrelia burgdorferi sensu stricto Spirochetes and Are not Affected by Ixodes ricinus Tick Saliva.

Lyme disease is a pathology caused by members of the Borrelia burgdorferi sensu lato (s.l.) complex, most often by B. burgdorferi sensu stricto (s.s.). They are transmitted mainly by Ixodes ricinus ticks. After a few hours of infestation, neutrophils massively infiltrate the bite site. They can kill Borrelia via phagocytosis, oxidative burst and hydrolytic enzymes. However, factors in tick saliva promote propagation of the bacteria in the host even in the presence of a large number of neutrophils. Neutrophil extracellular trap (NET) consists in the extrusion of the neutrophil’s own DNA, forming traps that can retain and kill bacteria. The production of reactive oxygen species (ROS) is apparently associated with the onset of NEtosis. Here we describe NETs formation at the tick bite site in vivo in mice. We show that Borrelia burgdorferi s.s. spirochetes become trapped and killed by NETs in humans and that the bacteria do not seem to release significant nucleases to evade this process. Saliva from I. ricinus did not affect NET formation by human neutrophiles or it stability. However, it strongly decreased neutrophil ROS production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation. Finally, round bodies were observed trapped in NETs, some of them staining as live cells. This observation could help contribute to a better explanation of erythema migrans

Proteostasis is essential during cochlear development for neuron survival and hair cell polarity

Protein homeostasis is essential to cell function, and a compromised ability to reduce the load of misfolded and aggregated proteins is linked to numerous age-related diseases, including hearing loss. Here, we show that altered proteostasis consequent to Elongator complex deficiency also impacts the proper development of the cochlea and results in deafness. In the absence of the catalytic subunit Elp3, differentiating spiral ganglion neurons display large aggresome-like structures and undergo apoptosis before birth. The cochlear mechanosensory cells are able to survive proteostasis disruption but suffer defects in polarity and stereociliary bundle morphogenesis. We demonstrate that protein aggregates accumulate at the apical surface of hair cells, where they cause a local slowdown of microtubular trafficking, altering the distribution of intrinsic polarity proteins and affecting kinocilium position and length. Alleviation of protein misfolding using the chemical chaperone 4-phenylbutyric acid during embryonic development ameliorates hair cell polarity in Elp3-deficient animals. Our study highlights the importance of developmental proteostasis in the cochlea and unveils an unexpected link between proteome integrity and polarized organization of cellular components. © 2019 The Author

An assessment of interactions between global health initiatives and country health systems

Since 2000, the emergence of several large disease-specific global health initiatives (GHIs) has changed the way in which international donors provide assistance for public health. Some critics have claimed that these initiatives burden health systems that are already fragile in countries with few resources, whereas others have asserted that weak health systems prevent progress in meeting disease-specific targets. So far, most of the evidence for this debate has been provided by speculation and anecdotes. We use a review and analysis of existing data, and 15 new studies that were submitted to WHO for the purpose of writing this Report to describe the complex nature of the interplay between country health systems and GHIs. We suggest that this Report provides the most detailed compilation of published and emerging evidence so far, and provides a basis for identification of the ways in which GHIs and health systems can interact to mutually reinforce their effects. On the basis of the findings, we make some general recommendations and identify a series of action points for international partners, governments, and other stakeholders that will help ensure that investments in GHIs and country health systems can fulfil their potential to produce comprehensive and lasting results in disease-specific work, and advance the general public health agenda. The target date for achievement of the health-related Millennium Development Goals is drawing close, and the economic downturn threatens to undermine the improvements in health outcomes that have been achieved in the past few years. If adjustments to the interactions between GHIs and country health systems will improve efficiency, equity value for money, and outcomes in global public health, then these opportunities should not be missed