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ATAC-Seq based chromatin accessibilty profile of human monocytes treated with MV130 or its excipient

ABSTRACT: MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. We showed that MV130 induces long term heterologous protection against viral respiratory infections in mice by a mechanism associated with the induction of trained immunity. Moreover, we found that MV130 induces reprogramming of in vitro human monocytes promoting metabolic changes and enhanced cytokine production. To assess the role of epigenetic changes in MV130-mediated trained immunity induction in human monocytes we measured the chromatin accessibility landscape using ATAC-seq.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183485 | GEO | 2021/11/10

REPOSITORIES: GEO

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ATAC-Seq based chromatin accessibilty profile of MPPs from mice treated with MV130 or its excipient

Project description:MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. We showed that MV130 induces long term heterologous protection against viral respiratory infections in mice. Moreover, intranasal administration of MV130 provided protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. As trained immunity acts via modulation of hematopoietic stem and progenitor cells (Kaufmann et al., 2018; Mitroulis et al., 2018) we hypothesized that MV130 could confer systemic long-term protection through reprogramming of hematopoietic precursors. For that we measured the chromatin accessibility landscape in multipotent progenitors (MPPs) coming from mice treated with MV130 or its excipient using ATAC-seq.

2021-11-10 | GSE183486 | GEO

Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections

Project description:MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Herein, we observe that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provided protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogated the protection conferred by MV130 against Influenza A virus respiratory infection. MV130 induced reprogramming of mouse bone marrow progenitor cells and human monocytes, promoting an enhanced cytokine production that relied on metabolic and epigenetic shifts. Our results unveil that the mucosal a dministration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity. This SuperSeries is composed of the SubSeries listed below.

2021-11-10 | GSE183721 | GEO

Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs [RNA-seq]

Project description:Respiratory viral infections reprogram pulmonary macrophages with altered anti-infectious functions. However, the potential function of virus-trained macrophages in antitumor immunity in the lung, a preferential target of both primary and metastatic malignancies, is not well understood. Using mouse models of influenza and lung metastatic tumors, we show here that influenza trains respiratory mucosal-resident alveolar macrophages (AMs) to exert long-lasting and tissue-specific antitumor immunity. Trained AMs infiltrate tumor lesions and have enhanced phagocytic and tumor cell cytotoxic functions, which are associated with epigenetic, transcriptional and metabolic resistance to tumor-induced immune suppression. Generation of antitumor trained immunity in AMs is dependent on interferon-γ and natural killer cells. Notably, human AMs with trained immunity traits in non-small cell lung cancer tissue are associated with a favorable immune microenvironment. These data reveal a function for trained resident macrophages in pulmonary mucosal antitumor immune surveillance. Induction of trained immunity in tissue-resident macrophages might thereby be a potential antitumor strategy.

2023-01-09 | GSE222149 | GEO

Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs [ATAC-seq]

2023-01-09 | GSE222148 | GEO

Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections

Project description:Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections

| PRJNA761724 | ENA

TLR-2-mediated activation of innate responses in the upper airways confers rapid anti-viral protection of the lungs

Project description:The impact of respiratory virus infections on global health is felt not just during a pandemic but for many, endemic seasonal infections pose an equal and ongoing risk of severe disease. Moreover, vaccines and antiviral drugs are not always effective or available for many respiratory viruses. We investigated how induction of effective and appropriate antigen independent innate immunity in the upper airways can prevent spread of respiratory virus infection to the vulnerable lower airways. Activation of Toll-like receptor-2 (TLR2), when restricted to the nasal turbinates results in prompt induction of innate immune-driven anti-viral responses through action of cytokines, chemokines and cellular activity in the upper but not the lower airways. We define how nasal epithelial cells and recruitment of macrophages work in concert and play pivotal roles to limit progression of influenza virus to the lungs and sustain protection for up to seven days. These results reveal underlying mechanisms of how control of viral infection in the upper airways can occur and also support the implementation of strategies that can activate TLR2 in nasal passages to provide rapid protection, especially for at-risk populations, against severe respiratory infection when vaccines and antiviral drugs are not always effective or available.

2021-06-08 | PXD023041 | Pride

The effect of beta-glucan - induced trained immunity on the transcriptomic profile of tumor-associated monocytes

Project description:Induction of trained immunity by beta-glucan has been shown to promote transcriptomic alterations in myeloid cells. Monocytes are involved in the immune responses against tumors. In this study, we performed RNA sequencing in tumor-infiltrated monocytes from mice in order to investigate the impact of trained immunity on the transcriptomic profile of monocytes in the tumor setting.

2020-10-30 | GSE139451 | GEO

Transcriptome and Epigenome Characterization of Long Term Trained Immunity in Cotrolled Human Malaria Model [RNA-seq]

Project description:Innate immune memory responses (also termed ‘trained immunity’) have been described in monocytes after BCG vaccination and after stimulation in vitro with microbial and endogenous ligands such as muramyl dipeptide, β-glucan, oxidized LDL, and MSU crystals. Whether clinical infections are also capable of inducing a trained immunity phenotype has not been studied. We evaluated whether Plasmodium falciparum infection can induce innate immune memory by assessing monocyte epigenetic, transcriptional and functional (cytokine production) programs from five volunteers undergoing controlled human malaria infection. During acute infection monocytes produced lower amounts of inflammatory cytokines upon secondary stimulation, but 36 days after malaria infection they produced significantly higher IL-6 and TNF-α in response to various stimuli. Furthermore, transcriptomic and epigenomic data analysis revealed a clear reprogramming of monocytes after malaria infection. Plasmodium challenge induces a long-term deposition of H3K4me3 at the promoter regions of several inflammatory genes of monocytes, these changes remaining stable for several weeks after infection. These findings demonstrate an epigenetic basis of trained immunity in the model of controlled in vivo human malaria infection.

2020-12-21 | GSE137043 | GEO

Transcriptome and Epigenome Characterization of Long Term Trained Immunity in Cotrolled Human Malaria Model [ChIP-seq]

2020-12-21 | GSE137042 | GEO

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

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