抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation.

mTOR Signaling in Growth Control and Disease

The metabolic syndrome

mTOR signaling in growth control and disease.

Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat-fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.

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Metabolic endotoxemia initiates obesity and insulin resistance

The present invention concerns a composition comprising at least one prophylactically or therapeutically active agent selected from the group consisting of attenuated Porphyromonas gingivalis, inactivated Porphyromonas gingivalis, a subunit of Porphyromonas gingivalis, a recombinant or isolated immunogenic polypeptide or peptide from Porphyromonas gingivalis or a c DNA from Porphyromonas gingivalis, for use as a vaccine for preventing or treating periodontitis, diabetes, obesity and/or complications thereof in a subject. The present invention also concerns an isolated antibody having specificity for Porphyromonas gingivalis for use for preventing or treating periodontitis, diabetes, obesity and/or complications thereof in a subject.

Vaccination against diabetes, obesity and complications thereof

We propose a novel method to cluster gene networks. Based on a dissimilarity built using correlation structures, we consider networks that connect all the genes based on the strength of their dissimilarity. The large number of genes require the use of the threshold to find sparse structures in the graph. in this work, using the notion of graph coreness, we identify clusters of genes which are central in the network. Then we estimate a network that has these genes as main hubs. We use this new representation to identify biologically meaningful clusters, and to highlight the importance of the nodes that compose the core structures based on biological interpretations.

Rémy Burcelin

Papers

Vaccination against diabetes, obesity and complications thereof

A new gene co-expression network analysis based on Core Structure Detection (CSD)

Le microbiote, après une décennie d’étude dans le domaine du diabète : qu’a-t-on appris, quelles pistes thérapeutiques ?