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Transcriptome analysis of Intestinal epithelial cells after Heligmosomoides polygyrus bakeri (Hpb) infection

ABSTRACT: Transcriptome analysis of Intestinal epithelial cells after Heligmosomoides polygyrus bakeri (Hpb) infection

PROVIDER: PRJNA826533 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18747248_1.fastq.gz	Fastqsanger.gz
	SRR18747248_2.fastq.gz	Fastqsanger.gz
	SRR18747249_1.fastq.gz	Fastqsanger.gz
	SRR18747249_2.fastq.gz	Fastqsanger.gz
	SRR18747250_1.fastq.gz	Fastqsanger.gz

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Excretory/secretory microRNAs from the gastrointestinal nematode Heligmosomoides polygyrus bakeri in culture.

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Project description:Intestinal dendritic cells (DC) orchestrate the adaptive immune response that balances protection against pathogens and tolerance towards harmless antigens. Yet, it remains largely unknown what molecular mechanisms underly this functional duality. Heligmosomoides polygyrus bakeri (Hpb) is a naturally occurring parasite in mice characterised by unique immune-evasion strategies that counter host protective immunity. Here, we utilised this unique infection environment to study mechanisms by which DC maintain the immune balance. In-depth characterisation of intestinal DC during Hpb infection revealed the emergence of distinct populations of DC that drive protective Th2 responses, versus others with immunoregulatory properties. We also identified that the skewing of intestinal DC towards immunoregulatory functions was due to TGFb signalling via endogenous sources or by Hpb-produced TGFb-mimic molecules. Thus, our results present a mechanistic explanation for Hpb’s ability to modulate the adaptive immune system. Furthermore, these data offer an example of how heterogeneity within the DC compartment can determine the simultaneous generation of both pro- and anti-inflammatory immune responses.

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Project description:Gastrointestinal helminths are a major health threat worldwide. Alternatively activated macrophages (AAMs) have been shown to contribute to host protection during secondary helminth infections. AAMs express effector molecules that depend on activation of the IL-4- or IL-13-induced transcription factor signal transducer and activator of transcription 6 (STAT6). However, the specific role of STAT6-regulated genes like Arginase-1 (Arg1) from AAMs or STAT6-regulated genes in other cell types for host protection remains unclear. To address this point, we generated mice expressing STAT6 only in macrophages (Mac-STAT6 mouse). In the model of Heligmosomoides polygyrus bakeri (Hpb) infection, Mac-STAT6 mice could not trap larvae in the submucosa of the small intestine after secondary infection. Further, mice lacking Arg1 in hematopoietic and endothelial cells were still protected from secondary Hpb infection. On the other hand, specific deletion of IL-4/IL-13 in T cells blunted AAM polarization, activation of intestinal epithelial cells (IECs) and protective immunity. Deletion of IL-4Rα on IEC also caused loss of larval trapping while AAM polarization remained intact. These results show that Th2-dependent and STAT6-regulated genes in IECs are required and AAMs are not sufficient for protection against secondary Hpb infection by mechanisms that remain to be investigated.

| S-EPMC10109486 | biostudies-literature

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