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With frequent host shifts involving the colonization of new hosts across large geographical ranges, crop pests are good models for examining the mechanisms of rapid colonization. The microbial partners of pest insects may also be involved in or affected by colonization processes, which has been little studied so far. We investigated the demographic history of the rosy apple aphid, Dysaphis plantaginea, a major pest of the cultivated apple (Malus domestica) in Europe, North Africa and North America, as well as the diversity of its microbiota. We genotyped a comprehensive sample of 714 colonies from Europe, Morocco and the US using mitochondrial (CytB and CO1), bacterial (16s rRNA and TrnpB), and 30 microsatellite markers. We detected five populations spread across the US, Morocco, Western and Eastern Europe and Spain. Populations showed weak genetic differentiation and high genetic diversity, except the ones from Morocco and North America that are likely the result of recent colonization events. Coalescent-based inferences revealed high levels of gene flow among populations during the colonization but did not allow determining the sequence of colonization of Europe, North America and Morroco by D. plantaginea, likely because of the weak genetic differentiation and the occurrence of gene flow among populations. We found that D. plantaginea rarely hosts other endosymbiotic bacteria than its obligate nutritional symbiont Buchnera aphidicola. This suggests that secondary endosymbionts did not play an important role in the rapid spread of the rosy apple aphid. These findings have fundamental importance for understanding pest colonization processes and implications for sustainable pest control programs.

ObjectiveThe intestinal epithelial barrier (IEB) restricts the passage of microbes and potentially harmful substances from the lumen through the paracellular space, and rupture of its integrity is associated with a variety of gastrointestinal disorders and extra-digestive diseases. Increased IEB permeability has been linked to disruption of metabolic homeostasis leading to obesity and type 2 diabetes. Interestingly, recent studies have uncovered compelling evidence that the AMP-activated protein kinase (AMPK) signaling pathway plays an important role in maintaining epithelial cell barrier function. However, our understanding of the function of intestinal AMPK in regulating IEB and glucose homeostasis remains sparse.MethodsWe generated mice lacking the two α1 and α2 AMPK catalytic subunits specifically in intestinal epithelial cells (IEC AMPK KO) and determined the physiological consequences of intestinal-specific deletion of AMPK in response to high-fat diet (HFD)-induced obesity. We combined histological, functional, and integrative analyses to ascertain the effects of gut AMPK loss on intestinal permeability in vivo and ex vivo and on the development of obesity and metabolic dysfunction. We also determined the impact of intestinal AMPK deletion in an inducible mouse model (i-IEC AMPK KO) by measuring IEB function, glucose homeostasis, and the composition of gut microbiota via fecal 16S rRNA sequencing.ResultsWhile there were no differences in in vivo intestinal permeability in WT and IEC AMPK KO mice, ex vivo transcellular and paracellular permeability measured in Ussing chambers was significantly increased in the distal colon of IEC AMPK KO mice. This was associated with a reduction in pSer425 GIV phosphorylation, a marker of leaky gut barrier. However, the expression of tight junction proteins in intestinal epithelial cells and pro-inflammatory cytokines in the lamina propria were not different between genotypes. Although the HFD-fed AMPK KO mice displayed suppression of the stress polarity signaling pathway and a concomitant increase in colon permeability, loss of intestinal AMPK did not exacerbate body weight gain or adiposity. Deletion of AMPK was also not sufficient to alter glucose homeostasis or the acute glucose-lowering action of metformin in control diet (CD)- or HFD-fed mice. CD-fed i-IEC AMPK KO mice also presented higher permeability in the distal colon under homeostatic conditions but, surprisingly, this was not detected upon HFD feeding. Alteration in epithelial barrier function in the i-IEC AMPK KO mice was associated with a shift in the gut microbiota composition with higher levels of Clostridiales and Desulfovibrionales.ConclusionsAltogether, our results revealed a significant role of intestinal AMPK in maintaining IEB integrity in the distal colon but not in regulating glucose homeostasis. Our data also highlight the complex interaction between gut microbiota and host AMPK.

Regulatory T cells (Tregs) play a major role in immune homeostasis and in the prevention of autoimmune diseases. It has been shown that c-Rel is critical in Treg thymic differentiation, but little is known on the role of NF-κB on mature Treg biology. We thus generated mice with a specific knockout of RelA, a key member of NF-κB, in Tregs. These mice developed a severe autoimmune syndrome with multi-organ immune infiltration and high activation of lymphoid and myeloid cells. Phenotypic and transcriptomic analyses showed that RelA is critical in the acquisition of the effector Treg state independently of surrounding inflammatory environment. Unexpectedly, RelA-deficient Tregs also displayed reduced stability and cells that had lost Foxp3 produced inflammatory cytokines. Overall, we show that RelA is critical for Treg biology as it promotes both the generation of their effector phenotype and the maintenance of their identity.

To the Editor: Drugs that block tumor necrosis factor (TNF) have been used with success in the treatment of different autoimmune and inflammatory diseases, such as rheumatoid arthritis, Crohn's disease [...]

Regions of the south-western Mediterranean basin were the focus of many studies since they have experienced a series of climate changes. The contribution of the North Atlantic Oscillation in precipitations is required to be analyzed with the aim to understand the possible hydrological changes. In this way, an analysis of precipitations along the coast of central Maghreb (Morocco, Algeria and Tunisia) was carried. The present analysis was performed using (1) The graphical method of information processing and (2) wavelet transform technique. Results can be summarized as the following. Results show a high drought observed in all studied regions since the med-eighties and a return of the wet period since year 2003. Moreover, we demonstrate significant links of precipitations with the North Atlantic Oscillation

The IL-2/JAK3/STAT-5 signaling pathway is involved on the initiation and maintenance of the transcription factor Foxp3 in regulatory T cells (Treg) and has been associated with demethylation of the intronic Conserved Non Coding Sequence-2 (CNS2). However, the role of the JAK/STAT pathway in controlling Foxp3 in the short term has been poorly investigated. Using two different JAK/STAT pharmacological inhibitors, we observed a detectable loss of Foxp3 after 10 min. of treatment that affected 70% of the cells after one hour. Using cycloheximide, a general inhibitor of mRNA translation, we determined that Foxp3, but not CD25, has a high turnover in IL-2 stimulated Treg. This reduction was correlated with a rapid reduction of Foxp3 mRNA. This loss of Foxp3 was associated with a loss in STAT-5 binding to the CNS2, which however remains demethylated. Consequently, Foxp3 expression returns to normal level upon restoration of basal JAK/STAT signaling in vivo. Reduced expression of several genes defining Treg identity was also observed upon treatment. Thus, our results demonstrate that Foxp3 has a rapid turn over in Treg partly controlled at the transcriptional level by the JAK/STAT pathway.