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Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads
Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, the global rate of TB-related deaths has increased for the first time in over a decade. We and others have previously shown that a resolved prior or concurrent influenza A virus infection in Myc...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502726/ https://www.ncbi.nlm.nih.gov/pubmed/37720210 http://dx.doi.org/10.3389/fimmu.2023.1240419 |
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author | Baker, Paul J. Amaral, Eduardo P. Castro, Ehydel Bohrer, Andrea C. Torres-Juárez, Flor Jordan, Cassandra M. Nelson, Christine E. Barber, Daniel L. Johnson, Reed F. Hilligan, Kerry L. Mayer-Barber, Katrin D. |
author_facet | Baker, Paul J. Amaral, Eduardo P. Castro, Ehydel Bohrer, Andrea C. Torres-Juárez, Flor Jordan, Cassandra M. Nelson, Christine E. Barber, Daniel L. Johnson, Reed F. Hilligan, Kerry L. Mayer-Barber, Katrin D. |
author_sort | Baker, Paul J. |
collection | PubMed |
description | Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, the global rate of TB-related deaths has increased for the first time in over a decade. We and others have previously shown that a resolved prior or concurrent influenza A virus infection in Mycobacterium tuberculosis (Mtb)-infected mice resulted in increased pulmonary bacterial burden, partly through type I interferon (IFN-I)-dependent mechanisms. Here we investigated whether SARS-CoV-2 (SCV2) co-infection could also negatively affect bacterial control of Mtb. Importantly, we found that K18-hACE2 transgenic mice infected with SCV2 one month before, or months after aerosol Mtb exposure did not display exacerbated Mtb infection-associated pathology, weight loss, nor did they have increased pulmonary bacterial loads. However, pre-existing Mtb infection at the time of exposure to the ancestral SCV2 strain in infected K18-hACE2 transgenic mice or the beta variant (B.1.351) in WT C57Bl/6 mice significantly limited early SCV2 replication in the lung. Mtb-driven protection against SCV2 increased with higher bacterial doses and did not require IFN-I, TLR2 or TLR9 signaling. These data suggest that SCV2 co-infection does not exacerbate Mtb infection in mice, but rather the inflammatory response generated by Mtb infection in the lungs at the time of SCV2 exposure restricts viral replication. |
format | Online Article Text |
id | pubmed-10502726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105027262023-09-16 Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads Baker, Paul J. Amaral, Eduardo P. Castro, Ehydel Bohrer, Andrea C. Torres-Juárez, Flor Jordan, Cassandra M. Nelson, Christine E. Barber, Daniel L. Johnson, Reed F. Hilligan, Kerry L. Mayer-Barber, Katrin D. Front Immunol Immunology Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, the global rate of TB-related deaths has increased for the first time in over a decade. We and others have previously shown that a resolved prior or concurrent influenza A virus infection in Mycobacterium tuberculosis (Mtb)-infected mice resulted in increased pulmonary bacterial burden, partly through type I interferon (IFN-I)-dependent mechanisms. Here we investigated whether SARS-CoV-2 (SCV2) co-infection could also negatively affect bacterial control of Mtb. Importantly, we found that K18-hACE2 transgenic mice infected with SCV2 one month before, or months after aerosol Mtb exposure did not display exacerbated Mtb infection-associated pathology, weight loss, nor did they have increased pulmonary bacterial loads. However, pre-existing Mtb infection at the time of exposure to the ancestral SCV2 strain in infected K18-hACE2 transgenic mice or the beta variant (B.1.351) in WT C57Bl/6 mice significantly limited early SCV2 replication in the lung. Mtb-driven protection against SCV2 increased with higher bacterial doses and did not require IFN-I, TLR2 or TLR9 signaling. These data suggest that SCV2 co-infection does not exacerbate Mtb infection in mice, but rather the inflammatory response generated by Mtb infection in the lungs at the time of SCV2 exposure restricts viral replication. Frontiers Media S.A. 2023-09-01 /pmc/articles/PMC10502726/ /pubmed/37720210 http://dx.doi.org/10.3389/fimmu.2023.1240419 Text en Copyright © 2023 Baker, Amaral, Castro, Bohrer, Torres-Juárez, Jordan, Nelson, Barber, Johnson, Hilligan and Mayer-Barber https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Baker, Paul J. Amaral, Eduardo P. Castro, Ehydel Bohrer, Andrea C. Torres-Juárez, Flor Jordan, Cassandra M. Nelson, Christine E. Barber, Daniel L. Johnson, Reed F. Hilligan, Kerry L. Mayer-Barber, Katrin D. Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads |
title | Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads |
title_full | Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads |
title_fullStr | Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads |
title_full_unstemmed | Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads |
title_short | Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads |
title_sort | co-infection of mice with sars-cov-2 and mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502726/ https://www.ncbi.nlm.nih.gov/pubmed/37720210 http://dx.doi.org/10.3389/fimmu.2023.1240419 |
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