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Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart

For over a century, it has been reported that primary influenza infection promotes the development of a lethal form of bacterial pulmonary disease. More recently, pneumonia events caused by both viruses and bacteria have been directly associated with cardiac damage. Importantly, it is not known whet...

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Autores principales: Platt, Maryann P., Lin, Yi-Han, Wiscovitch-Russo, Rosana, Yu, Yanbao, Gonzalez-Juarbe, Norberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725598/
https://www.ncbi.nlm.nih.gov/pubmed/35089061
http://dx.doi.org/10.1128/mbio.03257-21
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author Platt, Maryann P.
Lin, Yi-Han
Wiscovitch-Russo, Rosana
Yu, Yanbao
Gonzalez-Juarbe, Norberto
author_facet Platt, Maryann P.
Lin, Yi-Han
Wiscovitch-Russo, Rosana
Yu, Yanbao
Gonzalez-Juarbe, Norberto
author_sort Platt, Maryann P.
collection PubMed
description For over a century, it has been reported that primary influenza infection promotes the development of a lethal form of bacterial pulmonary disease. More recently, pneumonia events caused by both viruses and bacteria have been directly associated with cardiac damage. Importantly, it is not known whether viral-bacterial synergy extends to extrapulmonary organs such as the heart. Using label-free quantitative proteomics and molecular approaches, we report that primary infection with pandemic influenza A virus leads to increased Streptococcus pneumoniae translocation to the myocardium, leading to general biological alterations. We also observed that each infection alone led to proteomic changes in the heart, and these were exacerbated in the secondary bacterial infection (SBI) model. Gene ontology analysis of significantly upregulated proteins showed increased innate immune activity, oxidative processes, and changes to ion homeostasis during SBI. Immunoblots confirmed increased complement and antioxidant activity in addition to increased expression of angiotensin-converting enzyme 2. Using an in vitro model of sequential infection in human cardiomyocytes, we observed that influenza enhances S. pneumoniae cytotoxicity by promoting oxidative stress enhancing bacterial toxin-induced necrotic cell death. Influenza infection was found to increase receptors that promote bacterial adhesion, such as polymeric immunoglobulin receptor and fibronectin leucine-rich transmembrane protein 1 in cardiomyocytes. Finally, mice deficient in programmed necrosis (i.e., necroptosis) showed enhanced innate immune responses, decreased virus-associated pathways, and promotion of mitochondrial function upon SBI. The presented results provide the first in vivo evidence that influenza infection promotes S. pneumoniae infiltration, necrotic damage, and proteomic remodeling of the heart.
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spelling pubmed-87255982022-01-06 Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart Platt, Maryann P. Lin, Yi-Han Wiscovitch-Russo, Rosana Yu, Yanbao Gonzalez-Juarbe, Norberto mBio Observation For over a century, it has been reported that primary influenza infection promotes the development of a lethal form of bacterial pulmonary disease. More recently, pneumonia events caused by both viruses and bacteria have been directly associated with cardiac damage. Importantly, it is not known whether viral-bacterial synergy extends to extrapulmonary organs such as the heart. Using label-free quantitative proteomics and molecular approaches, we report that primary infection with pandemic influenza A virus leads to increased Streptococcus pneumoniae translocation to the myocardium, leading to general biological alterations. We also observed that each infection alone led to proteomic changes in the heart, and these were exacerbated in the secondary bacterial infection (SBI) model. Gene ontology analysis of significantly upregulated proteins showed increased innate immune activity, oxidative processes, and changes to ion homeostasis during SBI. Immunoblots confirmed increased complement and antioxidant activity in addition to increased expression of angiotensin-converting enzyme 2. Using an in vitro model of sequential infection in human cardiomyocytes, we observed that influenza enhances S. pneumoniae cytotoxicity by promoting oxidative stress enhancing bacterial toxin-induced necrotic cell death. Influenza infection was found to increase receptors that promote bacterial adhesion, such as polymeric immunoglobulin receptor and fibronectin leucine-rich transmembrane protein 1 in cardiomyocytes. Finally, mice deficient in programmed necrosis (i.e., necroptosis) showed enhanced innate immune responses, decreased virus-associated pathways, and promotion of mitochondrial function upon SBI. The presented results provide the first in vivo evidence that influenza infection promotes S. pneumoniae infiltration, necrotic damage, and proteomic remodeling of the heart. American Society for Microbiology 2022-01-04 /pmc/articles/PMC8725598/ /pubmed/35089061 http://dx.doi.org/10.1128/mbio.03257-21 Text en Copyright © 2022 Platt et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Observation
Platt, Maryann P.
Lin, Yi-Han
Wiscovitch-Russo, Rosana
Yu, Yanbao
Gonzalez-Juarbe, Norberto
Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart
title Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart
title_full Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart
title_fullStr Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart
title_full_unstemmed Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart
title_short Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart
title_sort pandemic influenza infection promotes streptococcus pneumoniae infiltration, necrotic damage, and proteomic remodeling in the heart
topic Observation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725598/
https://www.ncbi.nlm.nih.gov/pubmed/35089061
http://dx.doi.org/10.1128/mbio.03257-21
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