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Direct type I interferon signaling in hepatocytes controls malaria

Malaria is a devastating disease impacting over half of the world’s population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilit...

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Autores principales: Marques-da-Silva, Camila, Peissig, Kristen, Walker, Michael P., Shiau, Justine, Bowers, Carson, Kyle, Dennis E., Vijay, Rahul, Lindner, Scott E., Kurup, Samarchith P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422951/
https://www.ncbi.nlm.nih.gov/pubmed/35858541
http://dx.doi.org/10.1016/j.celrep.2022.111098
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author Marques-da-Silva, Camila
Peissig, Kristen
Walker, Michael P.
Shiau, Justine
Bowers, Carson
Kyle, Dennis E.
Vijay, Rahul
Lindner, Scott E.
Kurup, Samarchith P.
author_facet Marques-da-Silva, Camila
Peissig, Kristen
Walker, Michael P.
Shiau, Justine
Bowers, Carson
Kyle, Dennis E.
Vijay, Rahul
Lindner, Scott E.
Kurup, Samarchith P.
author_sort Marques-da-Silva, Camila
collection PubMed
description Malaria is a devastating disease impacting over half of the world’s population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, precluding the manipulation of such responses to combat malaria. Utilizing transcriptomics, infection studies, and a transgenic Plasmodium strain that exports and traffics Cre recombinase, we show that direct type I IFN signaling in Plasmodium-infected hepatocytes is necessary to control malaria. We also show that the majority of infected hepatocytes naturally eliminate Plasmodium infection, revealing the potential existence of anti-malarial cell-autonomous immune responses in such hepatocytes. These discoveries challenge the existing paradigms in Plasmodium immunobiology and are expected to inspire anti-malarial drugs and vaccine strategies.
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spelling pubmed-94229512022-08-29 Direct type I interferon signaling in hepatocytes controls malaria Marques-da-Silva, Camila Peissig, Kristen Walker, Michael P. Shiau, Justine Bowers, Carson Kyle, Dennis E. Vijay, Rahul Lindner, Scott E. Kurup, Samarchith P. Cell Rep Article Malaria is a devastating disease impacting over half of the world’s population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, precluding the manipulation of such responses to combat malaria. Utilizing transcriptomics, infection studies, and a transgenic Plasmodium strain that exports and traffics Cre recombinase, we show that direct type I IFN signaling in Plasmodium-infected hepatocytes is necessary to control malaria. We also show that the majority of infected hepatocytes naturally eliminate Plasmodium infection, revealing the potential existence of anti-malarial cell-autonomous immune responses in such hepatocytes. These discoveries challenge the existing paradigms in Plasmodium immunobiology and are expected to inspire anti-malarial drugs and vaccine strategies. 2022-07-19 /pmc/articles/PMC9422951/ /pubmed/35858541 http://dx.doi.org/10.1016/j.celrep.2022.111098 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Marques-da-Silva, Camila
Peissig, Kristen
Walker, Michael P.
Shiau, Justine
Bowers, Carson
Kyle, Dennis E.
Vijay, Rahul
Lindner, Scott E.
Kurup, Samarchith P.
Direct type I interferon signaling in hepatocytes controls malaria
title Direct type I interferon signaling in hepatocytes controls malaria
title_full Direct type I interferon signaling in hepatocytes controls malaria
title_fullStr Direct type I interferon signaling in hepatocytes controls malaria
title_full_unstemmed Direct type I interferon signaling in hepatocytes controls malaria
title_short Direct type I interferon signaling in hepatocytes controls malaria
title_sort direct type i interferon signaling in hepatocytes controls malaria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422951/
https://www.ncbi.nlm.nih.gov/pubmed/35858541
http://dx.doi.org/10.1016/j.celrep.2022.111098
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