Viral infection triggers interferon-induced expulsion of live Cryptococcus neoformans by macrophages

Paula Seoane Denicola, Leanne Taylor-Smith, David Stirling, Lucy C. K. Bell, Mahdad Noursadeghi, Dalan Bailey, Robin May

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
102 Downloads (Pure)

Abstract

Cryptococcus neoformans is an opportunistic human pathogen, which causes serious disease in immunocompromised hosts. Infection with this pathogen is particularly relevant in HIV+ patients, where it leads to around 200,000 deaths per annum. A key feature of cryptococcal pathogenesis is the ability of the fungus to survive and replicate within the phagosome of macrophages, as well as its ability to be expelled from host cells via a novel non-lytic mechanism known as vomocytosis. Here we show that cryptococcal vomocytosis from macrophages is strongly enhanced by viral coinfection, without altering phagocytosis or intracellular proliferation of the fungus. This effect occurs with distinct, unrelated human viral pathogens and is recapitulated when macrophages are stimulated with the anti-viral cytokines interferon alpha or beta (IFNα or IFNβ). Importantly, the effect is abrogated when type-I interferon signalling is blocked, thus underscoring the importance of type-I interferons in this phenomenon. Lastly, our data help resolve previous, contradictory animal studies on the impact of type I interferons on cryptococcal pathogenesis and suggest that secondary viral stimuli may alter patterns of cryptococcal dissemination in the host.
Original languageEnglish
Article numbere1008240
JournalPLoS pathogens
Volume16
Issue number2
DOIs
Publication statusPublished - 27 Feb 2020

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