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Gene expression profile at single cell level of cells from the lungs of Mock and MuHV-4 infected mice.

ABSTRACT: Gene expression profile at single cell level of cells from the lungs of Mock and MuHV-4 infected mice.

PROVIDER: PRJNA902798 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22325370.fastq.gz	Fastqsanger.gz
	SRR22325371.fastq.gz	Fastqsanger.gz
	SRR22325372.fastq.gz	Fastqsanger.gz
	SRR22325373.fastq.gz	Fastqsanger.gz
	SRR22325374.fastq.gz	Fastqsanger.gz

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Gene expression profile at single cell level of cells from the lungs of Mock and MuHV-4 infected mice.

Project description:The immunology of asthma is complex and involves the loss of immunoregulatory pathways with the adoption of a Western lifestyle inducing changes in the diversity and the time exposure to microorganisms. Gammaherpesviruses (γHVs) are among the most prevalent human viruses. Establishing early life infection, they profoundly imprint the immune system of their hosts. Using Murid herpesvirus 4 (MuHV-4), a mouse model of human γHV infections, we showed that both lung resident and bone marrow-derived group 2 innate lymphoid cells (ILC2s) displayed lasting reduced capacity to expand and to produce type 2 cytokines, in response to house dust mites, in an IFN-γ depend manner. Importantly, we uncovered that pulmonary ILC2s represent essential niche cells that imprint alveolar macrophage tissue-specific identity upon monocyte replenishment in infection settings. In particular, we showed that MuHV-4 infection disrupts the normal ILC2-epithelial cells circuit that imprints monocytes-derived AMs for type 2 functions without affecting their differentiation. These results reveal that persistent γHV infection shapes the alveolar landscape much beyond the initial acute infection through long-term effect on ILC2 niche cells.

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Gene expression profile at single cell level of cells from the lungs of Mock and MuHV-4 infected mice after HDM challenge.

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Gene expression profile at single cell level of cells from the lungs of Mock and MuHV-4 infected mice after HDM challenge.

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Gene expression profile at single cell level of monocytes (MOs) and T cells from the lungs and from broncho-alveolar lavage fluids (BALF) from Mock and MuHV-4 infected WT and CCR2 KO mice.

Project description:Gammaherpesviruses (γHVs) have co-evolved with their hosts over millions of years, leading to remarkably high infection prevalence and establishment of symbiotic relationship. Therefore, the lifelong persistence of γHVs appear to broadly shape host immunity. Here, we show that pulmonary infection with Murid herpesvirus 4 (MuHV-4), a mouse γHV, drives the recruitment in the airways of Ly6Chi monocytes (MOs) that control the host immune response. Indeed, the absence of those MOs elicits a severe virus-induced immunopathology associated with the systemic release of inflammatory mediators. Mechanistically, MuHV-4 imprinted MOs recruit CD4 T cells in the airways and trigger immunosuppressive signalling pathways through the PDL1/PD-1 axis, thereby dampening the deleterious activation of cytotoxic CD4 T cells. These results uncover a role for Ly6Chi MOs in the modulation of CD4 T cell functions, and reveal key pathways that could be targeted to interfere with the detrimental immunopathological cascade during respiratory viral infections.

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RNA profiles of cells in the lungs of MuHV-4 infected mice.

Project description:RNA profiles of cells in the lungs of MuHV-4 infected mice.

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Gene expression profile at single cell level of monocytes (MOs) and T cells from the lungs and from broncho-alveolar lavage fluids (BALF) from Mock and MuHV-4 infected WT and CCR2 KO mice.

Project description:Gene expression profile at single cell level of monocytes (MOs) and T cells from the lungs and from broncho-alveolar lavage fluids (BALF) from Mock and MuHV-4 infected WT and CCR2 KO mice.

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