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Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route

Despite the importance of the respiratory route for Brucella transmission, the lung immune response to this pathogen is scarcely characterized. We investigated the role of the cGAS/STING pathway of microbial DNA recognition in the control of respiratory Brucella infection. After in vitro B. abortus...

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Autores principales: Alonso Paiva, Iván M., A. Santos, Raiany, Brito, Camila B., Ferrero, Mariana C., Ortiz Wilczyñski, Juan Manuel, Silva, Eugenio A. Carrera, C. Oliveira, Sergio, Baldi, Pablo C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227575/
https://www.ncbi.nlm.nih.gov/pubmed/37261352
http://dx.doi.org/10.3389/fimmu.2023.1116811
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author Alonso Paiva, Iván M.
A. Santos, Raiany
Brito, Camila B.
Ferrero, Mariana C.
Ortiz Wilczyñski, Juan Manuel
Silva, Eugenio A. Carrera
C. Oliveira, Sergio
Baldi, Pablo C.
author_facet Alonso Paiva, Iván M.
A. Santos, Raiany
Brito, Camila B.
Ferrero, Mariana C.
Ortiz Wilczyñski, Juan Manuel
Silva, Eugenio A. Carrera
C. Oliveira, Sergio
Baldi, Pablo C.
author_sort Alonso Paiva, Iván M.
collection PubMed
description Despite the importance of the respiratory route for Brucella transmission, the lung immune response to this pathogen is scarcely characterized. We investigated the role of the cGAS/STING pathway of microbial DNA recognition in the control of respiratory Brucella infection. After in vitro B. abortus infection, CFU numbers were significantly higher in alveolar macrophages (AM) and lung explants from STING KO mice than in samples from wild type (WT) mice, but no difference was observed for cGAS KO samples. CFU were also increased in WT AM and lung epithelial cells preincubated with the STING inhibitor H151. Several proinflammatory cytokines (TNF-α, IL-1β, IL-6, IP-10/CXCL10) were diminished in Brucella-infected lung explants and/or AM from STING KO mice and cGAS KO mice. These cytokines were also reduced in infected AM and lung epithelial cells pretreated with H151. After intratracheal infection with B. abortus, STING KO mice exhibited increased CFU in lungs, spleen and liver, a reduced expression of IFN-β mRNA in lungs and spleen, and reduced levels of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and lung homogenates. Increased lung CFU and reduced BALF cytokines were also observed in cGAS KO mice. In summary, the cGAS/STING pathway induces the production of proinflammatory cytokines after respiratory Brucella infection, which may contribute to the STING-dependent control of airborne brucellosis.
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spelling pubmed-102275752023-05-31 Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route Alonso Paiva, Iván M. A. Santos, Raiany Brito, Camila B. Ferrero, Mariana C. Ortiz Wilczyñski, Juan Manuel Silva, Eugenio A. Carrera C. Oliveira, Sergio Baldi, Pablo C. Front Immunol Immunology Despite the importance of the respiratory route for Brucella transmission, the lung immune response to this pathogen is scarcely characterized. We investigated the role of the cGAS/STING pathway of microbial DNA recognition in the control of respiratory Brucella infection. After in vitro B. abortus infection, CFU numbers were significantly higher in alveolar macrophages (AM) and lung explants from STING KO mice than in samples from wild type (WT) mice, but no difference was observed for cGAS KO samples. CFU were also increased in WT AM and lung epithelial cells preincubated with the STING inhibitor H151. Several proinflammatory cytokines (TNF-α, IL-1β, IL-6, IP-10/CXCL10) were diminished in Brucella-infected lung explants and/or AM from STING KO mice and cGAS KO mice. These cytokines were also reduced in infected AM and lung epithelial cells pretreated with H151. After intratracheal infection with B. abortus, STING KO mice exhibited increased CFU in lungs, spleen and liver, a reduced expression of IFN-β mRNA in lungs and spleen, and reduced levels of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and lung homogenates. Increased lung CFU and reduced BALF cytokines were also observed in cGAS KO mice. In summary, the cGAS/STING pathway induces the production of proinflammatory cytokines after respiratory Brucella infection, which may contribute to the STING-dependent control of airborne brucellosis. Frontiers Media S.A. 2023-05-16 /pmc/articles/PMC10227575/ /pubmed/37261352 http://dx.doi.org/10.3389/fimmu.2023.1116811 Text en Copyright © 2023 Alonso Paiva, A. Santos, Brito, Ferrero, Ortiz Wilczyñski, Silva, C. Oliveira and Baldi 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
Alonso Paiva, Iván M.
A. Santos, Raiany
Brito, Camila B.
Ferrero, Mariana C.
Ortiz Wilczyñski, Juan Manuel
Silva, Eugenio A. Carrera
C. Oliveira, Sergio
Baldi, Pablo C.
Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route
title Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route
title_full Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route
title_fullStr Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route
title_full_unstemmed Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route
title_short Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route
title_sort role of the cgas/sting pathway in the control of brucella abortus infection acquired through the respiratory route
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227575/
https://www.ncbi.nlm.nih.gov/pubmed/37261352
http://dx.doi.org/10.3389/fimmu.2023.1116811
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