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Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation

Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This...

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Autores principales: Hilligan, Kerry L., Oyesola, Oyebola O., Namasivayam, Sivaranjani, Howard, Nina, Clancy, Chad S., Oland, Sandra D., Garza, Nicole L., Lafont, Bernard A. P., Johnson, Reed F., Mayer-Barber, Katrin D., Sher, Alan, Loke, P’ng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9665339/
https://www.ncbi.nlm.nih.gov/pubmed/36380767
http://dx.doi.org/10.1101/2022.11.09.515832
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author Hilligan, Kerry L.
Oyesola, Oyebola O.
Namasivayam, Sivaranjani
Howard, Nina
Clancy, Chad S.
Oland, Sandra D.
Garza, Nicole L.
Lafont, Bernard A. P.
Johnson, Reed F.
Mayer-Barber, Katrin D.
Sher, Alan
Loke, P’ng
author_facet Hilligan, Kerry L.
Oyesola, Oyebola O.
Namasivayam, Sivaranjani
Howard, Nina
Clancy, Chad S.
Oland, Sandra D.
Garza, Nicole L.
Lafont, Bernard A. P.
Johnson, Reed F.
Mayer-Barber, Katrin D.
Sher, Alan
Loke, P’ng
author_sort Hilligan, Kerry L.
collection PubMed
description Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This protection is associated with a lymphocytic infiltrate including an increased accumulation of pulmonary SCV2-specific CD8+ T cells and anti-CD8 antibody depletion abrogated the N. brasiliensis-mediated reduction in viral loads. Pulmonary macrophages with a type-2 transcriptional signature persist in the lungs of N. brasiliensis exposed mice after clearance of the parasite and establish a primed environment for increased antigen presentation. Accordingly, depletion of macrophages ablated the augmented viral clearance and accumulation of CD8+ T cells driven by prior N. brasiliensis infection. Together, these findings support the concept that lung migrating helminths can limit disease severity during SCV2 infection through macrophage-dependent enhancement of anti-viral CD8+ T cell responses.
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spelling pubmed-96653392022-11-15 Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation Hilligan, Kerry L. Oyesola, Oyebola O. Namasivayam, Sivaranjani Howard, Nina Clancy, Chad S. Oland, Sandra D. Garza, Nicole L. Lafont, Bernard A. P. Johnson, Reed F. Mayer-Barber, Katrin D. Sher, Alan Loke, P’ng bioRxiv Article Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This protection is associated with a lymphocytic infiltrate including an increased accumulation of pulmonary SCV2-specific CD8+ T cells and anti-CD8 antibody depletion abrogated the N. brasiliensis-mediated reduction in viral loads. Pulmonary macrophages with a type-2 transcriptional signature persist in the lungs of N. brasiliensis exposed mice after clearance of the parasite and establish a primed environment for increased antigen presentation. Accordingly, depletion of macrophages ablated the augmented viral clearance and accumulation of CD8+ T cells driven by prior N. brasiliensis infection. Together, these findings support the concept that lung migrating helminths can limit disease severity during SCV2 infection through macrophage-dependent enhancement of anti-viral CD8+ T cell responses. Cold Spring Harbor Laboratory 2022-11-10 /pmc/articles/PMC9665339/ /pubmed/36380767 http://dx.doi.org/10.1101/2022.11.09.515832 Text en https://creativecommons.org/publicdomain/zero/1.0/This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license (https://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Article
Hilligan, Kerry L.
Oyesola, Oyebola O.
Namasivayam, Sivaranjani
Howard, Nina
Clancy, Chad S.
Oland, Sandra D.
Garza, Nicole L.
Lafont, Bernard A. P.
Johnson, Reed F.
Mayer-Barber, Katrin D.
Sher, Alan
Loke, P’ng
Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation
title Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation
title_full Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation
title_fullStr Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation
title_full_unstemmed Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation
title_short Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation
title_sort helminth exposure protects against murine sars-cov-2 infection through macrophage dependent t cell activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9665339/
https://www.ncbi.nlm.nih.gov/pubmed/36380767
http://dx.doi.org/10.1101/2022.11.09.515832
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