Project description:A pressing clinical challenge is identifying the etiologic basis of acute respiratory illness. Without reliable diagnostics, the uncertainty associated with this clinical entity leads to a significant, inappropriate use of antibacterials. Use of host peripheral blood gene expression data to classify individuals with bacterial infection, viral infection, or non-infection represents a complementary diagnostic approach. Patients with respiratory tract infection along with ill, non-infected controls were enrolled through the emergency department or undergraduate student health services. Whole blood was obtained to generate gene expression profiles. These profiles were then used to generate signatures of bacterial acute respiratory infection, viral acute respiratory infection, and non-infectious illness.
Project description:A pressing clinical challenge is identifying the etiologic basis of acute respiratory illness. Without reliable diagnostics, the uncertainty associated with this clinical entity leads to a significant, inappropriate use of antibacterials. Use of host peripheral blood gene expression data to classify individuals with bacterial infection, viral infection, or non-infection represents a complementary diagnostic approach. Patients with respiratory tract infection along with ill, non-infected controls were enrolled through the emergency department or undergraduate student health services. Whole blood was obtained to generate gene expression profiles. These profiles were then used to generate signatures of bacterial acute respiratory infection, viral acute respiratory infection, and non-infectious illness. 273 subjects were ascertained for this analysis. This included 88 patients with non-infectious illness, 115 with viral acute respiratory infection, and 70 with bacterial acute respiratory infection. Samples were obtained at the time of enrollment, which was at initial clinical presentation. Total RNA was extracted from human blood using the PAXgene Blood RNA Kit. Microarray data were generated using the GeneChip Human Genome U133A 2.0 Array. Microarrays were generated in two microarray batches with seven overlapping samples giving rise to 280 total microarray experiments.
Project description:Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection.
Project description:The respiratory epithelium is the body’s first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
Project description:The respiratory epithelium is the body’s first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
Project description:The respiratory epithelium is the body’s first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
Project description:The respiratory epithelium is the body’s first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
Project description:The respiratory epithelium is the body’s first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
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.