Antigen-Presenting Cells Represent Targets for R5 HIV-1 Infection in the First Trimester Pregnancy Uterine Mucosa

BACKGROUND: During the first trimester of pregnancy, HIV-1 mother-to-child transmission is relatively rare despite the permissivity of placental cells to cell-to-cell HIV-1 infection. The placenta interacts directly with maternal uterine cells (decidual cells) but the physiological role of the decidua in the control of HIV-1 transmission and whether decidua could be a source of infected cells is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To answer to this question, decidual mononuclear cells were exposed to HIV-1 in vitro. Decidual cells were shown to be more susceptible to infection by an R5 HIV-1, as compared to an X4 HIV-1. Infected cells were identified by flow cytometry analysis. The results showed that CD14(+) cells were the main targets of HIV-1 infection in the decidua. These infected CD14(+) cells expressed DC-SIGN, CD11b, CD11c, the Fc gamma receptor CD16, CD32 and CD64, classical MHC class-I and class-II and maturation and activation molecules CD83, CD80 and CD86. The permissivity of decidual tissue was also evaluated by histoculture. Decidual tissue was not infected by X4 HIV-1 but was permissive to R5 HIV-1. Different profiles of infection were observed depending on tissue localization. CONCLUSIONS/SIGNIFICANCE: The presence of HIV-1 target cells in the decidua in vitro and the low rate of in utero mother-to-child transmission during the first trimester of pregnancy suggest that a natural control occurs in vivo limiting cell-to-cell infection of the placenta and consequently infection of the fetus

Seminal Plasma Exposures Strengthen Vaccine Responses in the Female Reproductive Tract Mucosae

HIV-1 sexual transmission occurs mainly via mucosal semen exposures. In the female reproductive tract (FRT), seminal plasma (SP) induces physiological modifications, including inflammation. An effective HIV-1 vaccine should elicit mucosal immunity, however, modifications of vaccine responses by the local environment remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized the impact of HIV-1+ SP intravaginal exposure on the local immune responses of non-human primates. Multiple HIV-1+ SP exposures did not impact the anti-MVA antibody responses. However, SP exposures revealed an anti-MVA responses mediated by CD4+ T cells, which was not observed in the control group. Furthermore, the frequency and the quality of specific anti-MVA CD8+ T cell responses increased in the FRT exposed to SP. Multi-parameter approaches clearly identified the cervix as the most impacted compartment in the FRT. SP exposures induced a local cell recruitment of antigen presenting cells, especially CD11c+ cells, and CD8+ T cell recruitment in the FRT draining lymph nodes. CD11c+ cell recruitment was associated with upregulation of inflammation-related gene expression after SP exposures in the cervix. We thus highlight the fact that physiological conditions, such as SP exposures, should be taken into consideration to test and to improve vaccine efficacy against HIV-1 and other sexually transmitted infections

Weed control method drives conservation tillage efficiency on farmland breeding birds

International audienceCrops management is known to influence biodiversity, especially conservation tillage (CT, no-till) often found as a positive method compared to conventional tillage (T, inversion of soil) but without controlling for underlying farming practices. There are many ways to perform CT, in particular concerning the control of weeds, but few studies have taken into account these methods, which could explain the lack of consensus about the effect of CT compared to T. We tested differences in breeding birds abundance between CT and T while accounting for weed control methods in oilseed rape and wheat CT fields. During the intercrop period, one CT system used a cover crop to control weeds (CTcc), the other used herbicides (CTh) and the control (T) system only used a tillage. We made CTcc/T and CTh/T comparisons by sampling bird abundance (respectively 49 CTcc/51 T and 30 CTh/33 T point counts). We show substantial differences between CTcc/T and CTh/T comparisons as we detected greater bird abundances in CTcc than T for 5 species (2.3–4.1 times more individuals) and a lower abundance in CTh than T for 2 species (2.1–2.2 times less individuals). Our results demonstrate the importance to account for system features to ensure the CT efficiency for farmland birds, declining strongly in Europe since 1980 (−55 to −67%). Results also highlight an even more negative impact of herbicides than tillage, showing that stopping tillage to intensify herbicide use is not a promising way

Data from: Tillage and herbicide reduction mitigate the gap between conventional and organic farming effects on foraging activity of insectivorous bats

The increased use of pesticides and tillage intensification is known to negatively affect biodiversity. Changes in these agricultural practices such as herbicide and tillage reduction have variable effects among taxa, especially at the top of the trophic network including insectivorous bats. Very few studies compared the effects of agricultural practices on such taxa, and overall, only as a comparison of conventional versus organic farming without accurately accounting for underlying practices, especially in conventional where many alternatives exist. Divergent results founded in these previous studies could be driven by this lack of clarification about some unconsidered practices inside both conventional and organic systems. We simultaneously compared, over whole nights, bat activity on contiguous wheat fields of one organic and three conventional farming systems located in an intensive agricultural landscape. The studied organic fields (OT) used tillage (i.e., inversion of soil) without chemical inputs. In studied conventional fields, differences consisted of the following: tillage using few herbicides (T), conservation tillage (i.e., no inversion of soil) using few herbicides (CT), and conservation tillage using more herbicide (CTH), to control weeds. Using 64 recording sites (OT = 12; T = 21; CT = 13; CTH = 18), we sampled several sites per system placed inside the fields each night. We showed that bat activity was always higher in OT than in T systems for two (Pipistrellus kuhlii and Pipistrellus pipistrellus) of three species and for one (Pipistrellus spp.) of two genera, as well as greater species richness. The same results were found for the CT versus T system comparison. CTH system showed higher activity than T for only one genus (Pipistrellus spp.). We did not detect any differences between OT and CT systems, and CT showed higher activity than CTH system for only one species (Pipistrellus kuhlii). Activity in OT of Pipistrellus spp. was overall 3.6 and 9.3 times higher than CTH and T systems, respectively, and 6.9 times higher in CT than T systems. Our results highlight an important benefit of organic farming and contrasted effects in conventional farming. That there were no differences detected between the organic and one conventional system is a major result. This demonstrates that even if organic farming is presently difficult to implement and requires a change of economic context for farmers, considerable and easy improvements in conventional farming are attainable, while maintaining yields and approaching the ecological benefits of organic methods

Tillage and herbicide reduction mitigate the gap between conventional and organic farming effects on foraging activity of insectivorous bats

The increased use of pesticides and tillage intensification is known to negatively affect biodiversity. Changes in these agricultural practices such as herbicide and tillage reduction have variable effects among taxa, especially at the top of the trophic network including insectivorous bats. Very few studies compared the effects of agricultural practices on such taxa, and overall, only as a comparison of conventional versus organic farming without accurately accounting for underlying practices, especially in conventional where many alternatives exist. Divergent results founded in these previous studies could be driven by this lack of clarification about some unconsidered practices inside both conventional and organic systems. We simultaneously compared, over whole nights, bat activity on contiguous wheat fields of one organic and three conventional farming systems located in an intensive agricultural landscape. The studied organic fields (OT) used tillage (i.e., inversion of soil) without chemical inputs. In studied conventional fields, differences consisted of the following: tillage using few herbicides (T), conservation tillage (i.e., no inversion of soil) using few herbicides (CT), and conservation tillage using more herbicide (CTH), to control weeds. Using 64 recording sites (OT = 12; T = 21; CT = 13; CTH = 18), we sampled several sites per system placed inside the fields each night. We showed that bat activity was always higher in OT than in T systems for two (Pipistrellus kuhlii and Pipistrellus pipistrellus) of three species and for one (Pipistrellus spp.) of two genera, as well as greater species richness. The same results were found for the CT versus T system comparison. CTH system showed higher activity than T for only one genus (Pipistrellus spp.). We did not detect any differences between OT and CT systems, and CT showed higher activity than CTH system for only one species (Pipistrellus kuhlii). Activity in OT of Pipistrellus spp. was overall 3.6 and 9.3 times higher than CTH and T systems, respectively, and 6.9 times higher in CT than T systems. Our results highlight an important benefit of organic farming and contrasted effects in conventional farming. That there were no differences detected between the organic and one conventional system is a major result. This demonstrates that even if organic farming is presently difficult to implement and requires a change of economic context for farmers, considerable and easy improvements in conventional farming are attainable, while maintaining yields and approaching the ecological benefits of organic methods

Estimating habitat loss due to wind turbine avoidance by bats: Implications for European siting guidance

International audienceWind energy is rapidly growing as a renewable source of energy but is not neutral for wildlife, especially bats. Whereas most studies have focused on bat mortality through collision, very few have quantified the loss of habitat use resulting from the potential negative impact of wind turbines, and none of them for hub heights higher than 55 m. Such impacts could durably affect populations, creating a need for improvement of knowledge to integrate this concern in implementation strategies. We quantified the impact of wind turbines at different distances on the activity of 11 bat taxa and 2 guilds. We compared bat activity at hedgerows (207 sites) located at a distance of 0–1000 m from wind turbines (n = 151) of 29 wind farms in an agricultural region in the autumn (overall 193,980 bat passes) using GLMMs. We found a significant negative effect of proximity to turbines on activity for 3 species (Barbastella barbastellus, Nyctalus leisleiri, Pipistrellus pipistrellus), 2 species-groups (Myotis spp., Plecotus spp.) and 2 guilds (fast-flying and gleaner). Bat activity within 1000 m of wind turbines by gleaners and fast-flying bats is reduced by 53.8% and 19.6%, respectively. Our study highlighted that European recommendations (at least 200 m from any wooded edge) to limit mortality events likely strongly underestimate the loss of bat activity. The current situation is particularly worrying, with 89% of 909 turbines established in a region that does not comply with recommendations, which themselves are far from sufficient to limit the loss of habitat use

Evidence for two phylogenetic clusters within hepatitis C virus (HCV) genotype 2 inferred from analysis of complete coding sequences of 15 HCV strains.

International audienceThe aim of this study was to gain further insight into the evolution and classification of hepatitis C virus (HCV) by assessing the subtype distribution of 273 genotype 2 strains isolated from French blood donors from 1990 to 2010 and by determining complete coding sequences in subtype 2 strains. These classified into 7 of the established subtypes and into 15 additional lineages not yet assigned to a known subtype. Phylogenetic tree construction showed two well-supported clusters. Cluster 1 included most subtype 2 strains while cluster 2 included subtype 2l and one unassigned subtype 2. Full genome sequencing was performed on 15 genotype 2 strains belonging to both clusters, that is, one subtype 2b, two subtype 2c, three subtype 2i, two subtype 2j, one subtype 2k, two subtype 2l, and four unassigned strains. Genomes included a 9042- to 9108-nucleic acid open reading frame coding for a polyprotein comprising 3014-3036 amino acids. Mean nucleotide distances between subtypes belonging to the first cluster was 20.2 ± 1.4% while the mean distance between the two clusters was 25.9 ± 0.3%. Analysis indicated that the bifurcation between subtype 2l and other subtype 2 strains occurred early in the evolutionary process. Subtype 2l retained a genomic feature characteristic of non-genotype 2, that is, absence of the 60-nucleotide insertion in the NS5A region. This finding suggests that appearance and fixation of this insertion occurred late in the evolutionary history of HCV type 2 and that its absence is an ancestral feature of HCV

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Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms

Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm

Salmonella Typhimurium uses the Cpx stress response to detect N -chlorotaurine and promote the repair of oxidized proteins

International audienceThe cell envelope of gram-negative bacteria constitutes the first protective barrier between a cell and its environment. During host infection, the bacterial envelope is subjected to several stresses, including those induced by reactive oxygen species (ROS) and reactive chlorine species (RCS) produced by immune cells. Among RCS, N- chlorotaurine ( N- ChT), which results from the reaction between hypochlorous acid and taurine, is a powerful and less diffusible oxidant. Here, using a genetic approach, we demonstrate that Salmonella Typhimurium uses the CpxRA two-component system to detect N -ChT oxidative stress. Moreover, we show that periplasmic methionine sulfoxide reductase (MsrP) is part of the Cpx regulon. Our findings demonstrate that MsrP is required to cope with N -ChT stress by repairing N -ChT-oxidized proteins in the bacterial envelope. By characterizing the molecular signal that induces Cpx when S. Typhimurium is exposed to N -ChT, we show that N -ChT triggers Cpx in an NlpE-dependent manner. Thus, our work establishes a direct link between N -ChT oxidative stress and the envelope stress response