Melissa Bedard, Sanne van der Niet, Elliott M Bernard, Gregory Babunovic, Tan-Yun Cheng, Beren Aylan, Anita E Grootemaat, Sahadevan Raman, Laure Botella, Eri Ishikawa, Mary P O'Sullivan, Seónadh O'Leary, Jacob A Mayfield, Jeffrey Buter, Adriaan J Minnaard, Sarah M Fortune, Leon O Murphy, Daniel S Ory, Joseph Keane, Sho Yamasaki, Maximiliano G Gutierrez, Nicole van der Wel, D Branch Moody
Induction of lipid-laden foamy macrophages is a cellular hallmark of tuberculosis (TB) disease, which involves the transformation of infected phagolysosomes from a site of killing into a nutrient-rich replicative niche. Here, we show that a terpenyl nucleoside shed from Mycobacterium tuberculosis, 1-tuberculosinyladenosine (1-TbAd), caused lysosomal maturation arrest and autophagy blockade, leading to lipid storage in M1 macrophages. Pure 1-TbAd, or infection with terpenyl nucleoside-producing M. tuberculosis, caused intralysosomal and peribacillary lipid storage patterns that matched both the molecules and subcellular locations known in foamy macrophages...
March 15, 2023: Journal of Clinical Investigation