Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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
_version_ 1785106380370214912
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
work_keys_str_mv AT bakerpaulj coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT amaraleduardop coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT castroehydel coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT bohrerandreac coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT torresjuarezflor coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT jordancassandram coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT nelsonchristinee coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT barberdaniell coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT johnsonreedf coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT hilligankerryl coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads
AT mayerbarberkatrind coinfectionofmicewithsarscov2andmycobacteriumtuberculosislimitsearlyviralreplicationbutdoesnotaffectmycobacterialloads