Autophagy has been postulated to play role in mammalian host defense against fungal pathogens, although the molecular details remain unclear. Here, we show that primary macrophages deficient in the autophagic factor LC3 demonstrate diminished fungicidal activity but increased cytokine production in response to Candida albicans stimulation. LC3 recruitment to fungal phagosomes requires activation of the fungal pattern receptor dectin-1. LC3 recruitment to the phagosome also requires Syk signaling but is independent of all activity by Toll-like receptors and does not require the presence of the adaptor protein Card9. We further demonstrate that reactive oxygen species generation by NADPH oxidase is required for LC3 recruitment to the fungal phagosome. These observations directly link LC3 to the inflammatory pathway against C. albicans in macrophages.
Background: Dectin-1 is able to recognize and phagocytose the fungal carbohydrate, -1,3-glucan, but its contribution to phagosomal maturation has not been explored. Results: Dectin-1-dependent Syk activation promotes phagolysosomal fusion and acidification. Conclusion: Dectin-1-dependent Syk-activation permits egress of early phagosomes to mature phagolysosomes. Significance: The surface recognition receptor, Dectin-1 shapes anti-fungal responses by controlling fungal phagosome maturation.
BackgroundResearch has explored associations between diet, body weight, and the food environment; however, few studies have examined historical trends in food environments.MethodsIn the Framingham Heart Study Offspring (N = 3321) and Omni (N = 447) cohorts, we created food environment metrics in four Massachusetts towns utilizing geocoded residential, workplace, and food establishment addresses from 1971 to 2008. We created multilevel models adjusted for age, sex, education, and census tract poverty to examine trends in home, workplace, and commuting food environments.ResultsProximity to and density of supermarkets, fast-food, full service restaurants, convenience stores, and bakeries increased over time for residential, workplace, and commuting environments; exposure to grocery stores decreased. The greatest increase in access was for supermarkets, with residential distance to the closest supermarket 1406 m closer (95% CI 1303 m, 1508 m) by 2005–2008 than in 1971–1975. Although poorer census tracts had higher access to fast-food restaurants consistently across follow-up, this disparity dissipated over time, due to larger increases in proximity to fast-food in wealthier neighborhoods.ConclusionsAccess to most food establishment types increased over time, with similar trends across home, workplace, and commuter environments.Electronic supplementary materialThe online version of this article (doi:10.1186/s12966-017-0537-4) contains supplementary material, which is available to authorized users.
Objectives To examine whether traffic-light labeling and choice architecture interventions improved dietary choices among students at a northeastern US university. Methods In 6 cafeterias at Harvard University, in Cambridge, Massachusetts, we implemented a 7-week intervention including traffic-light labeling (red: least nutrient rich; yellow: nutrient neutral; green: most nutrient rich), choice architecture (how choices are presented to consumers), and “healthy-plate” tray stickers. During the 2014–2015 academic year, 2 cafeterias received all interventions, 2 received choice architecture only, and 2 were controls. We analyzed sales for 6 weeks before and 7 weeks during interventions. Using interrupted time-series analyses, we measured changes in red, yellow, and green items served. We collected 1329 surveys to capture perceptions of labeling. Results Among 2.6 million portions served throughout the study, we found no significant changes in red (−0.8% change/week; P = .2) or green (+1.1% change/week; P = .4) items served at intervention sites compared with controls. In surveys, 58% of students reported using traffic-light labels at least a few times per week, and 73% wanted them to continue. Conclusions Although many students reported using traffic-light labels regularly and wanted interventions to continue, cafeteria interventions did not demonstrate clear improvements in dietary quality.
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