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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:130

Enthalten in:

The Journal of clinical investigation - 130(2020), 7 vom: 01. Juli, Seite 3805-3819

Sprache:

Englisch

Beteiligte Personen:

Dragotakes, Quigly [VerfasserIn]
Stouffer, Kaitlin M [VerfasserIn]
Fu, Man Shun [VerfasserIn]
Sella, Yehonatan [VerfasserIn]
Youn, Christine [VerfasserIn]
Yoon, Olivia Insun [VerfasserIn]
De Leon-Rodriguez, Carlos M [VerfasserIn]
Freij, Joudeh B [VerfasserIn]
Bergman, Aviv [VerfasserIn]
Casadevall, Arturo [VerfasserIn]

Links:

Volltext

Themen:

Cell Biology
Fungal infections
Immunology
Innate immunity
Journal Article
Macrophages
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 02.02.2021

Date Revised 19.03.2024

published: Print

Citation Status MEDLINE

doi:

10.1172/JCI133938

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM308831217