IL-1 and IL-23 Mediate Early IL-17A Production in Pulmonary Inflammation Leading to Late Fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+) γδ T cells and to a lesser extent by CD4αβ(+) T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. CONCLUSIONS: Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology

BMC Med

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates

Architecture of an Antagonistic Tree/Fungus Network: The Asymmetric Influence of Past Evolutionary History

Compartmentalization and nestedness are common patterns in ecological networks. The aim of this study was to elucidate some of the processes shaping these patterns in a well resolved network of host/pathogen interactions.Based on a long-term (1972-2005) survey of forest health at the regional scale (all French forests; 15 million ha), we uncovered an almost fully connected network of 51 tree taxa and 157 parasitic fungal species. Our analyses revealed that the compartmentalization of the network maps out the ancient evolutionary history of seed plants, but not the ancient evolutionary history of fungal species. The very early divergence of the major fungal phyla may account for this asymmetric influence of past evolutionary history. Unlike compartmentalization, nestedness did not reflect any consistent phylogenetic signal. Instead, it seemed to reflect the ecological features of the current species, such as the relative abundance of tree species and the life-history strategies of fungal pathogens. We discussed how the evolution of host range in fungal species may account for the observed nested patterns.Overall, our analyses emphasized how the current complexity of ecological networks results from the diversification of the species and their interactions over evolutionary times. They confirmed that the current architecture of ecological networks is not only dependent on recent ecological processes

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

La procalcitonine reste-t-elle un marqueur d'infection au cours des états de choc en réanimation ?

LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Ecological integration of alien species into a tree-parasitic fungus network

The diversification of species and their interactions during the course of evolution has produced ecological networks with a complex topology. This topology influences the current functioning of ecosystems. It is therefore important to investigate whether the species introduced recently by human activities have merged seamlessly into recipient ecological networks by developing interactions quantitatively and qualitatively similar to those of native species, or whether their establishment has altered the topology of the networks. We tackled this issue in the case of a well resolved interaction network between 51 forest tree taxa and 154 pathogenic fungal species. We found that alien and native species with similar phylogenetic histories and life-history strategies had similar types and numbers of interactions. Our results also suggest that the clustered architecture of the network has not been altered by the integration of alien species. It therefore seems that a few centuries have been sufficient for the network to assimilate the newly introduced species. This rapid integration was unexpected for a plant-pathogen network, because selection acts continually on plants, favouring the emergence of defences against new pathogens and impeding the development of new interactions. However, it was recently shown that perturbation of the structure of ecological networks might be overlooked if species interactions are not quantified. The tree-parasitic fungus network considered in this study is binary. We might therefore end up with different results by using quantitative data

Spatial variability of phyllosphere fungal assemblages: genetic distance predominates over geographic distance in a European beech stand (Fagus syluatica)

Despite being major drivers of the dynamics and diversity of plant populations and communities, the spatial variability of phyllosphere fungal assemblages has been seldom explored. We used CE-SSCP and 454 pyrosequencing to quantify the spatial variability of European beech phyllosphere fungal assemblages with a hierarchical sampling design including four different spatial scales (tree, branch, group of leaves and individual leaf). Fungal assemblages were highly diverse, with high proportions of generalist and cosmopolitan fungi. The major part of the variability was at the smallest spatial scale, between individual leaves. Within a single tree canopy, dissimilarity between fungal assemblages generally increased with distance between leaves. This pattern may be driven by within-canopy gradients of leaf traits and microclimate. At the stand scale, dissimilarity between fungal assemblages was correlated with the genetic distance rather than the geographic distance between trees, consistent with the findings of community genetics studies. Our results were constant over a small simulated sequencing depth, providing opportunities for the design of large-scale studies addressing the relationship between the genetic variation of trees and the variation of associated phyllosphere fungal assemblages

Distribution of parasitic fungal species richness: influence of climate versus host species diversity

One major challenge in parasitology and epidemiology is determining whether the richness of parasitic and infectious diseases simply tracks host diversity or is largely determined by exogenous factors, such as climate-forced variables. We addressed this issue by analysing a 30-year survey of fungal diseases in French forests. We first combined generalized linear models and stepwise analyses to select the habitat descriptors that may account for variations in parasitic fungal species richness. Our results suggest that host species diversity is not a major determinant of parasite richness. Temperature seasonality, host abundance, and the composition of host species assemblages may play a greater role. Then we used structural equation modelling to investigate the links between these habitat descriptors and parasitic fungal species richness. Our results showed that climatic and host species descriptors had not only direct effects on species richness, but also indirect effects (via host species and sampling effort, respectively). Our results also showed that the direct effects of climate and host species were roughly equal. We therefore conclude that it is important to take into account exogenous factors when investigating the potential causes of spatial variation in the richness of parasitic diseases, in particular for plant disease

The composition of phyllosphere fungal assemblages of European beech (Fagus sylvatica) varies significantly along an elevation gradient

Little is known about the potential effect of climate warming on phyllosphere fungi, despite their important impact on the dynamics and diversity of plant communities. The structure of phyllosphere fungal assemblages along elevation gradients may provide information about this potential effect, because elevation gradients correspond to temperature gradients over short geographic distances. We thus investigated variations in the composition of fungal assemblages inhabiting the phyllosphere of European beech (Fagus sylvatica) at four sites over a gradient of 1000 m of elevation in the French Pyrenees Mountains, by using tag-encoded 454 pyrosequencing. Our results show that the composition of fungal assemblages varied significantly between elevation sites, in terms of both the relative abundance and the presenceabsence of species, and that the variations in assemblage composition were well correlated with variations in the average temperatures. Our results therefore suggest that climate warming might alter both the incidence and the abundance of phyllosphere fungal species, including potential pathogens. For example, Mycosphaerella punctiformis, a causal agent of leaf spots, showed decreasing abundance with elevation and might therefore shift to higher elevations in response to warming