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Intergenerational inheritance of trained immunity and heterologous resistance to infections

ABSTRACT: Intergenerational inheritance of trained immunity and heterologous resistance to infections

PROVIDER: PRJNA535502 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15647612.fastq.gz	Fastqsanger.gz
	SRR15647613.fastq.gz	Fastqsanger.gz
	SRR15647614.fastq.gz	Fastqsanger.gz
	SRR15647615.fastq.gz	Fastqsanger.gz
	SRR15647616.fastq.gz	Fastqsanger.gz

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Intergenerational inheritance of trained immunity and heterologous resistance to infections (ATAC-seq)

Project description:Intergenerational inheritance (Inter-I) of phenotypic characteristics has been demonstrated in plants and invertebrates, with epigenetic modifications playing a role in the inheritance of a variety of features such as appearance1, adaptation to stress, or resistance to infections. Here we provide evidence of Inter-I of transcriptional and epigenetic signatures of trained immunity to the progeny of mice that survived a sublethal systemic Candida albicans infection. Intergenerational trained mice (F1) presented with significant cellular, developmental, transcriptional, and epigenetic changes within the bone marrow resident myeloid effector and progenitor cell compartment. These alterations led to an enhanced responsiveness to in vivo endotoxin challenge and Escherichia coli infection, providing the offspring with protection against heterologous infections. These results argue for the contribution of Lamarckian evolutionary processes to protect against infections in vertebrates.

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Intergenerational inheritance of trained immunity and heterologous resistance to infections

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

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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.

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Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder

Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5â halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of âepigenetic carrierâ that mediate intergenerational inheritance of acquired traits. Mature sperm small-RNA profiles between High-fat-diet (HFD) and Normal-diet (ND) males; Transcriptional profiles of 8-cell embryos and balstocysts that developed from zygotes that injected with sperm RNAs from HFD vs ND males. Transcriptional profiles and RRBS profiles of islets of F1 offsrping that generated from zygotes that injected with sperm RNAs from HFD vs ND males.

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