Macrophages use a bet-hedging strategy for antimicrobial activity in phagolysosomal acidification

التفاصيل البيبلوغرافية
العنوان: Macrophages use a bet-hedging strategy for antimicrobial activity in phagolysosomal acidification
المؤلفون: Christine Youn, Arturo Casadevall, Yehonatan Sella, Aviv Bergman, Kaitlin M. Stouffer, Carlos M. De Leon-Rodriguez, Quigly Dragotakes, Man Shun Fu, Joudeh B. Freij, Olivia Insun Yoon
المصدر: J Clin Invest
سنة النشر: 2019
مصطلحات موضوعية: 0301 basic medicine, PH reduction, Phagolysosome, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Phagosomes, Organelle, Macrophage, Animals, Humans, Phagocytic Cell, Organism, Cryptococcus neoformans, Innate immune system, biology, Chemistry, Macrophages, General Medicine, Cryptococcosis, Hydrogen-Ion Concentration, biology.organism_classification, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Research Article
الوصف: Microbial ingestion by a macrophage results in the formation of an acidic phagolysosome but the host cell has no information on the pH susceptibility of the ingested organism. This poses a problem for the macrophage and raises the fundamental question of how the phagocytic cell optimizes the acidification process to prevail. We analyzed the dynamical distribution of phagolysosomal pH in murine and human macrophages that had ingested live or dead Cryptococcus neoformans cells, or inert beads. Phagolysosomal acidification produced a range of pH values that approximated normal distributions, but these differed from normality depending on ingested particle type. Analysis of the increments of pH reduction revealed no forbidden ordinal patterns, implying that the phagosomal acidification process was a stochastic dynamical system. Using simulation modeling, we determined that by stochastically acidifying a phagolysosome to a pH within the observed distribution, macrophages sacrificed a small amount of overall fitness to gain the benefit of reduced variation in fitness. Hence, chance in the final phagosomal pH introduces unpredictability to the outcome of the macrophage-microbe, which implies a bet-hedging strategy that benefits the macrophage. While bet hedging is common in biological systems at the organism level, our results show its use at the organelle and cellular level.
تدمد: 1558-8238
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b1210625905424358282de6eca93620
https://pubmed.ncbi.nlm.nih.gov/32298242
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....7b1210625905424358282de6eca93620
قاعدة البيانات: OpenAIRE