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Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection

ABSTRACT: Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection

PROVIDER: PRJNA849180 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19649800.fastq.gz	Fastqsanger.gz
	SRR19649801.fastq.gz	Fastqsanger.gz
	SRR19649802.fastq.gz	Fastqsanger.gz
	SRR19649803.fastq.gz	Fastqsanger.gz
	SRR19649798.fastq.gz	Fastqsanger.gz

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Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection

Project description:Influenza associated bacterial super-infections have devastating impacts on the lung and can result in increased risk of mortality. New strains of influenza circulate throughout the population yearly promoting the establishment of immune memory. Nearly all individuals have some degree of influenza memory prior to adulthood. Due to this we sought to understand the role of immune memory during bacterial super-infections. An influenza heterotypic immunity model was established using influenza A/PR/8/34 and A/X31. We report here that influenza experienced mice are more resistant to secondary bacterial infection with methicillin-resistant Staphylococcus aureus as determined by wasting, bacterial burden, pulmonary inflammation, and lung leak, despite significant ongoing lung remodeling. Multidimensional flow cytometry and lung transcriptomics revealed significant alterations in the lung environment in influenza-experienced mice compared with naïve animals. These include changes in the lung monocyte and T cell compartments, characterized by increased expansion of influenza tetramer specific CD8+ T cells. The protection that was seen in memory experienced mouse model is associated with the reduction in inflammatory mechanisms making the lung less susceptible to damage and subsequent bacterial colonization. These findings provide insight into how influenza heterotypic immunity re-shapes the lung environment and the immune response to a re-challenge event, which is highly relevant to the context of human infection.

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Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection.

Project description:Influenza-associated bacterial superinfections have devastating impacts on the lung and can result in increased risk of mortality. New strains of influenza circulate throughout the population yearly, promoting the establishment of immune memory. Nearly all individuals have some degree of influenza memory before adulthood. Due to this, we sought to understand the role of immune memory during bacterial superinfections. An influenza heterotypic immunity model was established using influenza A/Puerto Rico/8/34 and influenza A/X31. We report in this article that influenza-experienced mice are more resistant to secondary bacterial infection with methicillin-resistant Staphylococcus aureus as determined by wasting, bacterial burden, pulmonary inflammation, and lung leak, despite significant ongoing lung remodeling. Multidimensional flow cytometry and lung transcriptomics revealed significant alterations in the lung environment in influenza-experienced mice compared with naive animals. These include changes in the lung monocyte and T cell compartments, characterized by increased expansion of influenza tetramer-specific CD8+ T cells. The protection that was seen in the memory-experienced mouse model is associated with the reduction in inflammatory mechanisms, making the lung less susceptible to damage and subsequent bacterial colonization. These findings provide insight into how influenza heterotypic immunity reshapes the lung environment and the immune response to a rechallenge event, which is highly relevant to the context of human infection.

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Immunization with two heterotypic influenza hemagglutinins by time difference effectively produces broadly binding antibodies against heterotypic influenza virus

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