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Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation

ABSTRACT: Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation

PROVIDER: PRJNA978108 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24785818.fastq.gz	Fastqsanger.gz
	SRR24785819.fastq.gz	Fastqsanger.gz
	SRR24785820.fastq.gz	Fastqsanger.gz
	SRR24785821.fastq.gz	Fastqsanger.gz
	SRR24785822.fastq.gz	Fastqsanger.gz

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Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation

Project description:The initial exposure to pathogens and commensals confers innate immune cells the capacity to respond distinctively upon a second stimulus. This training capacity might play key functions in developing an adequate innate immune response to the continuous exposure to bacteria. However, the mechanisms involved in induction of trained immunity by commensals remain mostly unexplored. A. muciniphila represents an attractive candidate to study the promotion of these long-term responses. Here, we show that priming of macrophages with live A. muciniphila enhances bacterial intracellular survival and decreases the release of pro- and anti-inflammatory signals, lowering the production of TNF and IL-10. Global transcriptional analysis of macrophages after a secondary exposure to the bacteria showed the transcriptional rearrangement underpinning the phenotype observed compared to acutely exposed cells, with the increased expression of genes related to phagocytic capacity and those involved in the metabolic adjustment conducing to innate immune training. Accordingly, key genes related to bacterial killing and pro-inflammatory pathways were downregulated. These data demonstrate the importance of specific bacterial members in the modulation of local long-term innate immune responses, broadening our knowledge of the association between gut microbiome commensals and trained immunity as well as the anti-inflammatory probiotic potential of A. muciniphila.

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Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation.

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Project description:Akkermansia muciniphila, a common member of the human gut microbiota, is considered to be a beneficial resident of the intestinal mucus layer. Surface-exposed molecules produced by this organism likely play important roles in colonization and communication with other microbes and the host, but the protein composition of the outer membrane has not been characterized thus far. Herein we identify A. muciniphila proteins after enrichment and fractionation of the outer membrane proteome of A. muciniphila.

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