Seoane, PI;
Taylor-Smith, LM;
Stirling, D;
Bell, LCK;
Noursadeghi, M;
Bailey, D;
May, RC;
(2020)
Viral infection triggers interferon-induced expulsion of live Cryptococcus neoformans by macrophages.
PLOS Pathogens
, 16
(2)
, Article e1008240. 10.1371/journal.ppat.1008240.
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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.
| Type: | Article |
|---|---|
| Title: | Viral infection triggers interferon-induced expulsion of live Cryptococcus neoformans by macrophages |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.ppat.1008240 |
| Publisher version: | https://doi.org/10.1371/journal.ppat.1008240 |
| Language: | English |
| Additional information: | Copyright © 2020 Seoane et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Macrophages, Cryptococcus, Cryptococcus neoformans, HIV infections, Interferons, Fungi, Fungal pathogens, Viral transmission and infection |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10093157 |
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