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Heterogeneity in antiviral responses in the upper respiratory tract promotes differential non-lytic clearance of influenza viruses

ABSTRACT: Heterogeneity in antiviral responses in the upper respiratory tract promotes differential non-lytic clearance of influenza viruses

PROVIDER: PRJNA606054 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11068170.fastq.gz	Fastqsanger.gz
	SRR11068171.fastq.gz	Fastqsanger.gz
	SRR11068172.fastq.gz	Fastqsanger.gz
	SRR11068173.fastq.gz	Fastqsanger.gz
	SRR11878456.fastq.gz	Fastqsanger.gz

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Heterogeneity in antiviral responses in the upper respiratory tract promotes differential non-lytic clearance of influenza viruses

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Heterogeneity of Antiviral Responses in the Upper Respiratory Tract Mediates Differential Non-lytic Clearance of Influenza Viruses.

Project description:Influenza viruses initiate infection in the upper respiratory tract (URT), but early viral tropism and the importance of cell-type-specific antiviral responses in this tissue remain incompletely understood. By infecting transgenic lox-stop-lox reporter mice with a Cre-recombinase-expressing influenza B virus, we identify olfactory sensory neurons (OSNs) as a major viral cell target in the URT. These cells become infected, then eliminate the virus and survive in the host post-resolution of infection. OSN responses to infection are characterized by a strong induction of interferon-stimulated genes and more rapid clearance of viral protein relative to other cells in the epithelium. We speculate that this cell-type-specific response likely serves to protect the central nervous system from infection. More broadly, these results highlight the importance of evaluating antiviral responses across different cell types, even those within the same tissue, to more fully understand the mechanisms of viral disease.

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Project description:Phage therapy is a therapeutic approach to treat multidrug resistant infections that employs lytic bacteriophages (phages) to eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there is scarce data regarding its effects on the human host. Here, we aimed to understand how lytic phages interact with cells of the airway epithelium, the tissue site that is colonized by bacterial biofilms in numerous chronic respiratory disorders. Using a panel of Pseudomonas aeruginosa phages and human airway epithelial cells derived from a person with cystic fibrosis, we determined that interactions between phages and epithelial cells depend on specific phage properties as well as physiochemical features of the microenvironment. Although poor at internalizing phages, the airway epithelium responds to phage exposure by changing its transcriptional profile and secreting antiviral and proinflammatory cytokines that correlate with specific phage families. Overall, our findings indicate that mammalian responses to phages are heterogenous and could potentially alter the way that respiratory local defenses aid in bacterial clearance during phage therapy. Thus, besides phage receptor specificity in a particular bacterial isolate, the criteria to select lytic phages for therapy should be expanded to include mammalian cell responses.

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Non-lytic clearance of influenza B virus from infected cells

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Single-cell microglial transcriptomics during demyelination defines a microglial state required for lytic carcass clearance

Project description:How microglia respond and regulate demyelination is not fully understood. To understand how microglia respond during demyelination, we fed mice cuprizone and assessed the response of genetically fate-mapped microglia. Cuprizone-induced demyelination generated a robust microglial response. We conducted single-cell RNA sequencing and identified several cuprizone-associated microglia (CAM) clusters during demyelination. These clusters expressed a transcriptomic signature indicative of cytokine regulation and reactive oxygen species production with altered lysosomal and metabolic changes consistent with ongoing phagocytosis. To understand how microglia contribute to the clearance of dead oligodendrocytes, we ablated microglia starting at the peak of cell death. We used the viability dye acridine orange and monitored apoptotic and lytic cell morphologies after microglial ablation and found that microglia preferentially phagocytose lytic carcasses. In culture, microglia exposed to lytic carcasses partially recapitulated the CAM state, suggesting that phagocytosis contributes to this distinct microglial state during cuprizone demyelination.

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