Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis

Mata, E. (Universidad de Zaragoza) ; Tarancon, R. ; Guerrero, C. (Universidad de Zaragoza) ; Moreo, E. (Universidad de Zaragoza) ; Moreau, F. ; Uranga, S. (Universidad de Zaragoza) ; Gomez, A.B. (Universidad de Zaragoza) ; Marinova, D. (Universidad de Zaragoza) ; Domenech, M. ; Gonzalez-Camacho, F. ; Monzon, M. (Universidad de Zaragoza) ; Badiola, J. (Universidad de Zaragoza) ; Dominguez-Andres, J. ; Yuste, J ; Anel, A. (Universidad de Zaragoza) ; Peixoto, A. (Universidad de Zaragoza) ; Martin, C. ; Aguilo, N.

Resumen: 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.

Idioma: Inglés

DOI: 10.1126/sciimmunol.abc2934

Año: 2021

Publicado en: Science Immunology 6, 63 (2021)
ISSN: 2470-9468

Factor impacto JCR: 30.658 (2021)

Categ. JCR: IMMUNOLOGY rank: 5 / 162 = 0.031 (2021) - Q1 - T1

Factor impacto CITESCORE: 25.5 - Immunology and Microbiology (Q1) - Medicine (Q1)

Factor impacto SCIMAGO: 11.962 - Immunology and Allergy (Q1) - Immunology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/Construyendo Europa desde Aragón
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097625-B-I00

Tipo y forma: Article (Published version)

Área (Departamento): Área Microbiología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)