6 research outputs found
Biocompatible Packagings for Fully Implantable Multi-Panel Devices for Remote Monitoring of Metabolism
This paper compares three different biocompatible packagings suitable to support full implantation of multi-panel sensors for remote monitoring of metabolism. The three packagings have been designed, realized and implanted in mice for 30 days. ATP and neutrophil concentrations have been measured at the implant site after the device was explanted, to assess the level of biocompatibility of the device
ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in peyer's patches to promote host-microbiota mutualism
Microbial colonization of the gut induces the development of gut-associated lymphoid tissue (GALT). The molecular mechanisms that regulate GALT function and result in gut-commensal homeostasis are poorly defined. T follicular helper (Tfh) cells in Peyer's patches (PPs) promote high-affinity IgA responses. Here we found that the ATP-gated ionotropic P2X7 receptor controls Tfh cell numbers in PPs. Lack of P2X7 in Tfh cells enhanced germinal center reactions and high-affinity IgA secretion and binding to commensals. The ensuing depletion of mucosal bacteria resulted in reduced systemic translocation of microbial components, lowering B1 cell stimulation and serum IgM concentrations. Mice lacking P2X7 had increased susceptibility to polymicrobial sepsis, which was rescued by Tfh cell depletion or administration of purified IgM. Thus, regulation of Tfh cells by P2X7 activity is important for mucosal colonization, which in turn results in IgM serum concentrations necessary to protect the host from bacteremia
T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP
© 2017 The Authors The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer's patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help
Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis
Through an in vivo model of high susceptibility to MTB infection in DBA/2 mice, we utilized a multi-omic approach to show that caloric restriction (CR) is able to control pulmonary MTB infection and associated inflammatory damage through an immunometabolic reprogramming and enhanced anti-MTB capacity of immune cells. These data candidate CR as a novel strategy in the management of MTB infection in countries where TB is rapidly increasing in association with over-nutrition and obesity