ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/090/SRR26515990/SRR26515990_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/086/SRR26515986/SRR26515986_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/082/SRR26515982/SRR26515982_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/093/SRR26515993/SRR26515993_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/094/SRR26515994/SRR26515994_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/092/SRR26515992/SRR26515992_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/089/SRR26515989/SRR26515989_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/087/SRR26515987/SRR26515987_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/083/SRR26515983/SRR26515983_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/095/SRR26515995/SRR26515995_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/089/SRR26515989/SRR26515989_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/088/SRR26515988/SRR26515988_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/082/SRR26515982/SRR26515982_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/085/SRR26515985/SRR26515985_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/091/SRR26515991/SRR26515991_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/094/SRR26515994/SRR26515994_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/097/SRR26515997/SRR26515997_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/084/SRR26515984/SRR26515984_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/092/SRR26515992/SRR26515992_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/088/SRR26515988/SRR26515988_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/083/SRR26515983/SRR26515983_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/095/SRR26515995/SRR26515995_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/096/SRR26515996/SRR26515996_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/093/SRR26515993/SRR26515993_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/086/SRR26515986/SRR26515986_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/091/SRR26515991/SRR26515991_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/085/SRR26515985/SRR26515985_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/097/SRR26515997/SRR26515997_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/096/SRR26515996/SRR26515996_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/090/SRR26515990/SRR26515990_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/087/SRR26515987/SRR26515987_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR265/084/SRR26515984/SRR26515984_1.fastq.gzprimaryOK200GenomicsMcGill Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1032017Mus musculusxref:PubMed:38225437After a century of the Bacillus Calmette-Guérin (BCG) vaccine, our understanding of its protection against homologous (Mycobacterium tuberculosis) or heterologous (e.g. influenza virus) infections is still limited. Here we show that systemic (intravenous) BCG vaccination (BCG-iv) provides significant protection against subsequent influenza A virus (IAV) infection in mice. We further demonstrate that the BCG-mediated cross-protection against IAV is largely due to the enrichment of conventional CD4+ αβ effector memory T cells that express high levels of CX3CR1hi in circulation trafficking into the lung parenchyma. Importantly, pulmonary CX3CR1hi T cells limit early viral infection in an antigen-independent manner via potent IFNγ production, which subsequently enhances long-term antimicrobial activity of the innate immune system like alveolar macrophages. Similarly, we uncover a prominent IFNγ signature in which its increased basal production was associated with enhanced BCG-mediated heterologous innate memory responses in BCG-vaccinated humans. These results offer insight into the unknown mechanism by which BCG has persistently displayed broad protection against non-tuberculous infections via a crosstalk between adaptive and innate memory responses. Overall design: BCG vaccination administered intravenously generated a significant enrichment of effector memory T cells chracterized by their CX3CR1hi surface marker expression. Our data provides evidence that the expansion of these cells is key in the subsequent cross-protection between BCG vaccination and influenza infection. The increase in numbers of these cells in BCG-iv mice is evident, however asssessing the transcriptional profile of these cells can reveal any functional signature of the induction of memory T cells by BCG. We thus vaccinated mice with BCG-iv in paralell with PBS controls and after 28 days, purified CX3CR1lo and CX3CR1hi splenic T cells. We subjected the cells to Bulk-RNAseq and assessed the transcriptional landscape.ENAfalseBCG induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-y mediated trained immunityBCG induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-y mediated trained immunity2025-09-242023-11-02PRJNA1032017GSE2462011009038225437