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Thermotolerance in the pathogen Cryptococcus neoformans is linked to antigen masking via mRNA decay-dependent reprogramming
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Thermotolerance in the pathogen Cryptococcus neoformans is linked to antigen masking via mRNA decay-dependent reprogramming
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Journal Article
Thermotolerance in the pathogen Cryptococcus neoformans is linked to antigen masking via mRNA decay-dependent reprogramming
2019
Overview
A common feature shared by systemic fungal pathogens of environmental origin, such as
Cryptococcus neoformans
, is their ability to adapt to mammalian core body temperature. In
C. neoformans
, this adaptation is accompanied by Ccr4-mediated decay of ribosomal protein mRNAs. Here we use the related, but thermo-intolerant species
Cryptococcus amylolentus
to demonstrate that this response contributes to host-temperature adaptation and pathogenicity of cryptococci. In a
C. neoformans ccr4
Δ mutant, stabilized ribosomal protein mRNAs are retained in the translating pool, and stress-induced transcriptomic changes are reduced in comparison with the wild type strain, likely due to ineffective translation of transcription factors. In addition, the mutant displays increased exposure of cell wall glucans, and recognition by Dectin-1 results in increased phagocytosis by lung macrophages, linking mRNA decay to adaptation and immune evasion.
The fungal pathogen
Cryptococcus neoformans
can adapt to mammalian core body temperature. Here, Bloom et al. show that Ccr4-mediated decay of ribosomal protein mRNAs is important for thermotolerance and immune evasion by promoting masking of cell wall glucans.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 14/63
/ 38/88
/ 38/91
/ 45/71
/ 64/60
/ 96/47
/ Animals
/ Antigens
/ Antigens, Fungal - immunology
/ Cryptococcus neoformans - genetics
/ Cryptococcus neoformans - immunology
/ Cryptococcus neoformans - metabolism
/ Decay
/ Gene Expression Regulation, Fungal
/ Glucans
/ Humanities and Social Sciences
/ Lectins, C-Type - immunology
/ Macrophages, Alveolar - immunology
/ Masking
/ Mice
/ Proteins
/ Ribosomal Proteins - genetics
/ Science
