165909 20260116150735.0 doi 10.1126/sciimmunol.abc2934 sideral 126402 ART-2021-126402 eng Mata, E. Universidad de Zaragoza Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis 2021 Access copy available to the general public Unrestricted Bacillus Calmette-Guerin (BCG) is an attenuated bacterial vaccine used to protect against Mycobacterium tuberculosis (Mtb) in regions where infections are highly prevalent. BCG is currently delivered by the intradermal route, but alternative routes of administration are of great interest, including intrapulmonary delivery to more closely mimic respiratory Mtb infection. In this study, mice subjected to pulmonary delivery of green fluorescent protein-tagged strains of virulent (Mtb) and attenuated (BCG) mycobacteria were studied to better characterize infected lung cell subsets. Profound differences in dissemination patterns were detected between Mtb and BCG, with a strong tendency of Mtb to disseminate from alveolar macrophages (AMs) to other myeloid subsets, mainly neutrophils and recruited macrophages. BCG mostly remained in AMs, which promoted their activation. These preactivated macrophages were highly efficient in containing Mtb bacilli upon challenge and disrupting early bacterial dissemination, which suggests a potential mechanism of protection associated with pulmonary BCG vaccination. Respiratory BCG also protected mice against a lethal Streptococcus pneumoniae challenge, suggesting that BCG-induced innate activation could confer heterologous protection against respiratory pathogens different from Mtb. BCG drove long-term activation of AMs, even after vaccine clearance, and these AMs reacted efficiently upon subsequent challenge. These results suggest the generation of a trained innate memory-like response in AMs induced by pulmonary BCG vaccination. info:eu-repo/grantAgreement/ES/DGA-FEDER/Construyendo Europa desde Aragón info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097625-B-I00 info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 30.658 2021 IMMUNOLOGY 5 / 162 = 0.031 2021 Q1 T1 11.962 2021 Immunology and Allergy 2021 Q1 Immunology 2021 Q1 25.5 2021 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Tarancon, R. (orcid)0000-0002-3086-3013 Guerrero, C. Universidad de Zaragoza (orcid)0000-0002-7963-7797 Moreo, E. Universidad de Zaragoza (orcid)0000-0002-0182-201X Moreau, F. Uranga, S. Universidad de Zaragoza (orcid)0000-0001-7866-2803 Gomez, A.B. Universidad de Zaragoza (orcid)0000-0002-9713-2127 Marinova, D. Universidad de Zaragoza (orcid)0000-0001-8644-120X Domenech, M. Gonzalez-Camacho, F. Monzon, M. Universidad de Zaragoza (orcid)0000-0002-2787-9671 Badiola, J. Universidad de Zaragoza (orcid)0000-0002-7173-7216 Dominguez-Andres, J. Yuste, J Anel, A. Universidad de Zaragoza (orcid)0000-0002-5175-8394 Peixoto, A. Martin Montañés, C. Aguilo Anento, N. 1011 630 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Microbiología 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1011 X Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Proy. investigación HQA 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 6, 63 (2021) Sci. immunol. Science Immunology 2470-9468 3925772 http://zaguan.unizar.es/record/165909/files/texto_completo.pdf Postprint 1523183 http://zaguan.unizar.es/record/165909/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:165909 articulos driver 2026-01-16-15:06:10 ARTICLE