?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F39267%2F&rft.title=Glycolytic+Metabolism+of+Macrophages+Differs+by+Spatial+Location+and+Subset+in+Tuberculous+Granulomas&rft.creator=Gould%2C+Victoria&rft.description=Tuberculosis+(TB)%2C+caused+by+infection+with+Mycobacterium+tuberculosis+(Mtb)%2C+triggers+the+formation+of+granulomas+in+the+host.+Granulomas+are+composed+of+many+different+types+of+host+immune+cells+including+T+and+B+lymphocytes%2C+macrophages%2C+and+neutrophils+(PMN).+The+metabolic+pathways+used+by+immune+cells+in+granulomas+are+important+for+cell+function+and+glycolytic+metabolic+pathways+in+granulomas+may+be+involved+limiting+or+promoting+disease.+By+understanding+immunometabolism+in+TB+granulomas%2C+we+can+improve+diagnosis+and+potentially+create+new+therapeutics+to+combat+TB+disease.+GLUT1+is+a+glucose+transporter+that+transports+glucose+into+the+cell.+To+determine+what+cell+subsets+express+GLUT1+in+a+granuloma%2C+IHC+was+performed+on+lung+granuloma-containing+tissue+sections+from+non-human+primates+(NHP)+that+were+experimentally+infected+with+Mtb.+These+slides+were+stained+for+macrophage+markers+including+CD11c+and+CD163%2C+and+GLUT1%2C+before+being+imaged+by+fluorescence+microscopy.+Image+analysis+was+performed+using+ImageJ+to+determine+the+total+pixel+area+and+percent+pixel+area+of+each+cell+marker+occupied+in+granuloma+cross+sections%2C+as+well+as+co-localization+between+the+macrophage+markers+and+GLUT1.+To+identify+if+there+is+a+relationship+between+glucose+uptake+and+mycobacterial+antigens%2C+we+performed+a+glucose+uptake+assay+and+hypoxic+experiments+using+2-NBDG+on+monocyte-derived+macrophages+that+were+stimulated+with+inactivated+Mtb.+Image+analysis+revealed+co-localization+of+different+cell+markers+and+GLUT1.+When+looking+at+co-localization+of+CD11c+and+CD163+with+GLUT1%2C+we+found+that+CD11c%2BCD163-+epithelioid+macrophages%2C+the+cells+in+granulomas+that+are+most+commonly+infected+with+Mtb%2C+expressed+more+GLUT1+than+interstitial+and+alveolar+macrophages.+Moreover%2C+we+see+evidence+that+macrophages+increase+their+glucose+(2-NBDG)+uptake+when+stimulated+with+inactivated+Mtb.+Identifying+immune+cells+that+express+GLUT1+and+what+triggers+these+immune+cells+to+switch+to+glycolytic+metabolism+will+help+us+further+understand+overall+granuloma+metabolism+and+cell+differentiation+after+Mtb+infection.+In+terms+of+public+health%2C+by+better+understanding+the+immunometabolism+of+granulomas%2C+it+will+improve+monitoring+of+disease+progression+or+to+aid+in+the+treatment+of+Mtb+infection+to+help+reduce+tuberculosis+cases+worldwide.&rft.date=2020-07-30&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F39267%2F1%2FGouldV_thesis_6_2020.pdf&rft.identifier=++Gould%2C+Victoria++(2020)+Glycolytic+Metabolism+of+Macrophages+Differs+by+Spatial+Location+and+Subset+in+Tuberculous+Granulomas.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++