Summary Macrophages internalize pathogens through phagocytosis, entrapping them into organelles called phagosomes. Phagosomes then fuse with lysosomes to mature into phagolysosomes, acquiring an acidic and hydrolytic lumen that kills the pathogens. During an ongoing infection, macrophages can internalize dozens of bacteria. Thus, we hypothesized that an initial round of phagocytosis might boost lysosome function and bactericidal ability to cope with subsequent rounds of phagocytosis. To test this hypothesis, we employed Fcγ receptor-mediated phagocytosis and endocytosis, which respectively internalize immunoglobulin G (IgG)-opsonized particles and polyvalent IgG immune complexes. We report that Fcγ receptor activation in macrophages enhanced lysosome-based proteolysis and killing of subsequently phagocytosed E. coli compared to naïve macrophages. Importantly, we show that Fcγ receptor activation caused nuclear translocation of TFEB, a transcription factor that boosts expression of lysosome genes. Indeed, Fc receptor activation was accompanied by increased expression of specific lysosomal proteins. Remarkably, TFEB silencing repressed the Fcγ receptor-mediated enhancements in degradation and bacterial killing. In addition, nuclear translocation of TFEB required phagosome completion and failed to occur in cells silenced for MCOLN1, a lysosomal Ca2+ channel, suggesting that lysosomal Ca2+ released during phagosome maturation activates TFEB. Finally, we demonstrated that non-opsonic phagocytosis of E. coli also enhanced lysosomal degradation in a TFEB-dependent manner suggesting that this phenomenon is not limited to Fcγ receptors. Overall, we show that macrophages become better killers after one round of phagocytosis and suggest that phagosomes and lysosomes are capable of bi-directional signaling.
Drawing on exploratory research of online ethnographic records for particular types of Aboriginal bags in North America, we confront the absence of affective knowledge in museum catalogues and documentation. Although curatorial, ethnographic, and Aboriginal understandings of these items teem with affect, we find affect to be almost wholly lacking from available online records. We ask what the effects of this absence are for descendent Aboriginal communities, for museum publics, and for affect theory. We also look at an example where affect has a presence in online records, the Glenbow Museum, and consider the ways this creates opportunities for comparative and historic affective study.
Alexander Somerville (1811–85) was an extraordinary figure, notorious in his own lifetime for his espousal of political reform. The youngest child of impoverished farmers from the Scottish border country, he was the last soldier to be flogged publicly in Britain, after openly stating that his regiment would not fire on Reform agitators. In his subsequent journalistic career his stance was influenced by his concern that violent revolution would inevitably be crushed and so lead to greater suffering among the working class, and he therefore supported the less radical reform movement urged by Cobden. He was a passionate opponent of the Corn Laws, and The Whistler at the Plough (published in 1852) is a collection of his letters and essays for the Anti-Corn-Law League, based on information gathered during his own travels around the country. The volume also contains his eyewitness account of the Irish famine of 1847.
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