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Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis I

ABSTRACT: Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis I

PROVIDER: PRJNA880577 | ENA |

REPOSITORIES: ENA

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Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis II

Project description:Besides centrally induced innate immune memory/trained immunity in the bone marrow/peripheral blood by parenteral vaccination or infection, recently emerging evidence suggests that the barrier mucosal tissue-resident innate immune memory may develop via a local inflammatory pathway following mucosal immunologic exposure. However, it remains unclear whether the mucosal-resident innate immune memory may result from integrating distally generated immunological signals following parenteral vaccination/infection. We show here that subcutaneous Bacillus Calmette-Guérin (BCG) vaccination is able to induce memory alveolar macrophages (AM) and trained immunity at the respiratory barrier mucosa. Although parenteral BCG vaccine can centrally train bone marrow progenitors and circulating monocytes, induction of memory AM is entirely independent of circulating monocytes. Rather, parenteral BCG vaccination, via distal mycobacterial dissemination, causes a time-dependent alteration in gut microbiome, barrier function and microbial metabolites including short-chain fatty acids, and subsequently the changes in circulating and lung tissue metabolites, leading to induction of tissue-resident memory macrophages and trained innate immunity in the lung. Our study thus reveals a novel gut microbiota-mediated pathway for innate immune memory development at distal barrier mucosal tissues. Our findings have far-reaching implications in developing next-generation parenteral vaccine strategies against respiratory pathogens such as M.tb.

2022-09-16 | GSE213342 | GEO

Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis I

2022-09-16 | GSE213340 | GEO

Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis

Project description:Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis

| PRJNA880544 | ENA

Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis II

Project description:Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis II

| PRJNA880578 | ENA

Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination

Project description:Vaccination against tuberculosis by intradermal Bacillus Calmette-Guérin (BCG) injection saves many lives, supposedly by inducing adaptive immune memory in lymphocytes. Epidemiologically, BCG vaccination is also associated with reduced childhood mortality unrelated to TB, which is attributed to innate immune memory, also termed trained immunity. We recently demonstrated improved protection against tuberculosis infection in highly susceptible rhesus macaques by mucosal BCG vaccination, correlating with a unique local but no peripheral immune profile. Here, we investigated local and peripheral innate immune function after intradermal versus mucosal vaccination with M. bovis BCG or the live attenuated, M. tuberculosis-derived candidate, MTBVAC. The results demonstrate an augmented frequency of trained immunity in monocytes after respiratory mucosal administration of live attenuated mycobacterial vaccines compared to intradermal immunization, with MTBVAC being equally potent as BCG. These results provide further support to strategies for improving TB vaccination and, more broadly, modulating innate immunity via mucosal surfaces.

2021-01-27 | GSE159046 | GEO

Time-resolved transcriptomes of BCG vaccine induced trained immunity in human monocytes

2022-08-02 | GSE168468 | GEO

DNA methylation dynamics during monocyte-to-macrophage differentiation and BCG vaccine induced trained immunity

Project description:Trained immunity is a phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. This study profiled the transcriptomes of human monocytes responding to two different BCG vaccine strains.

2022-08-02 | GSE168628 | GEO

Parenteral BCG vaccine induces respiratory mucosal-resident memory macrophages and trained innate immunity via the gut-lung axis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-16 | GSE213343 | GEO

Time-resolved post-translational histone modifications during BCG vaccine induced trained immunity in human monocytes

2022-08-02 | GSE183528 | GEO

TRained Immunity induced by Bcg in UroThElial carcinoma (Tribute) associated epigenetic remodeling

Project description:Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. Intravesical instillation with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant therapy in patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC). HR-NMIBC is associated with a high risk of tumor recurrence and progression to muscle-invasive bladder cancer. The precise immunological mechanisms through which BCG mediates anti-tumor immunity are still unclear. The aim of our study was to investigate the (long-term) induction of trained immunity by repeated BCG instillations in NMIBC patients and elucidate the immunological and epigenetic mechanisms that are involved. Another aim was to assess the relationship between trained immunity response and clinical response of NMIBC patients, in terms of recurrence free survival and progression free survival. To determine whether BCG instillations induce trained immunity in peripheral blood mononuclear cells (PBMCs) we performed a prospective cohort study (‘Tribute’) and isolated PBMCs collected before BCG therapy and at 8 time points during BCG therapy. A total of 17 BCG-naïve HR-NMIBC patients were included. After isolation of PBMCs, monocytes were further purified using an isolation procotol with a percoll gradient. RNA was isolated from these purified monocytes were and used as input for RNA-seq analysis.

2023-03-30 | GSE190528 | GEO

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