Project description:Antibiotic resistance genes expressed in the upper respiratory tract of patients infected with influenza viruses were associated with the microbial community and microbial activities. Interactions between the host systemic responses to influenza infection and ARG expression highlight the importance of antibiotic resistance in viral-bacterial co-infection.
Project description:Antibiotic resistance genes expressed in the upper respiratory tract of patients infected with influenza viruses were associated with the microbial community and microbial activities. Interactions between the host systemic responses to influenza infection and ARG expression highlight the importance of antibiotic resistance in viral-bacterial co-infection.
Project description:Antibiotic resistance genes expressed in the upper respiratory tract of patients infected with influenza viruses were associated with the microbial community and microbial activities. Interactions between the host systemic responses to influenza infection and ARG expression highlight the importance of antibiotic resistance in viral-bacterial co-infection.
Project description:Seasonal influenza outbreaks represent a large burden for the healthcare system as well as the economy. While the role of the microbiome in the context of various diseases has been elucidated, the effects on the respiratory and gastrointestinal microbiome during influenza illness is largely unknown. Therefore, this study aimed to characterize the temporal development of the respiratory and gastrointestinal microbiome of swine using a multi-omics approach prior and during influenza infection. Swine is a suitable animal model for influenza research, as it is closely related to humans and a natural host for influenza viruses. Our results showed that IAV infection resulted in significant changes in the abundance of Moraxellaceae and Pasteurellaceae families in the upper respiratory tract. To our surprise, temporal development of the respiratory microbiome was not affected. Furthermore, we observed significantly altered microbial richness and diversity in the gastrointestinal microbiome after IAV infection. In particular, we found increased abundances of Prevotellaceae, while Clostridiaceae and Lachnospiraceae decreased. Furthermore, metaproteomics showed that the functional composition of the microbiome, known to be robust and stable under healthy conditions, was heavily affected by the influenza infection. Metabolome analysis proved increased amounts of short-chain fatty acids in the gastrointestinal tract, which might be involved in faster recovery. Furthermore, metaproteome data suggest a possible immune response towards flagellated Clostridia induced during the infection. Therefore, it can be assumed that the respiratory infection with IAV caused a systemic effect in the porcine host and microbiome.
Project description:Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 microbiome studies by analyzing the upper respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We found that time in the intensive care unit and the type of oxygen support explained the most variation within the upper respiratory tract microbiome, dwarfing (non-significant) effects from viral load, disease severity, and immune status. Specifically, mechanical ventilation was linked to altered community structure, lower species- and higher strain-level diversity, and significant shifts in oral taxa previously associated with COVID-19.
Project description:The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections. However, the pathologic contributors to influenza upper respiratory tissue pathology are incompletely understood. In this study, we investigated the role of IL-17RA as a modulator of influenza host response and inflammation in the upper respiratory tract. We used a combined experimental approach involving IL-17RA-/- mice and an air-liquid interface (ALI) epithelial culture model to investigate the role of IL-17 response in epithelial inflammation, barrier function, and tissue pathology. Our data show that IL-17RA-/- mice exhibited significantly reduced neutrophilia, epithelial injury, and viral load. The reduced NP inflammation and epithelial injury in IL-17RA-/- mice correlated with increased resistance against co-infection by Streptococcus pneumoniae (Spn). IL-17A treatment, while potentiating the apoptosis of IAV-infected epithelial cells, caused bystander cell death and disrupted the barrier function in ALI epithelial model, supporting the in vivo findings.
Project description:The determinants of influenza transmission remain poorly understood. Swine influenza viruses preferentially attach to receptors found in the upper airways; however, most swine influenza viruses fail to transmit efficiently from swine to humans, and from human-to-human. The pandemic 2009 H1N1 (H1N1pdm) virus was a rare exception of a swine virus that acquired efficient transmissibility from human-to-human, and is reflected in efficient respiratory droplet transmission in ferrets. We hypothesize that virus-induced host responses in the upper airways correlate with airborne transmission in ferrets. To address this question, we used the H1N1pdm virus and swine influenza A/swine/Hong Kong/201/2010 (HK201) virus that has comparable titre in the ferret nasopharynx, but it exhibits differential transmissibility in ferrets via respiratory droplet route. We performed a transcriptomic analysis of tissues from the upper and lower respiratory tract from ferrets infected with either H1N1pdm or HK201 viruses using ferret-specific Agilent oligonucleotide arrays. We found differences in the kinetics of the innate immune response elicited by these two viruses that varied across tissues.
Project description:Viral infections affecting the upper or lower respiratory tract induce mucin production in the epithelial surfaces of the respiratory cells. However, a little is known about how mucins are produced on the surfaces of respiratory epithelial cells and affects viral replication. In the course of the investigation of the cellular responses in the early stage of Influenza A virus (IAV) infection, we found that two miRNAs, miR-221 and miR-17-3p, which target the mRNA of GalNAc transferase 3 (GALNT3), are rapidly down-regulated as early as 1.5 h post-infection. To understand the early host cell responses to the IAV infection, we performed miRNA microarray analysis using a human alveolar adenocarcinoma cell line, A549 cells, infected with influenza A/Puerto Rico/8/34 H1N1 (PR8) virus. We isolated the cellular RNAs at 0.5, 1.5 and 4.5 h post-infection and detected significant changes in the global profile of miRNA expression after infection with IAV. mouse embryonic fibroblasts. Each sample was run in duplicate.