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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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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. |
format | Online Article Text |
id | pubmed-9422951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
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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