Research Interests:
Research Interests: Innate immunity, Neonatology, Inflammatory Immune Response, Humans, Mice, and 12 moreAnimals, Lung Diseases, Dendritic cell, Inflammatory disease, Clinical Sciences, Newborn Infant, SURFACTANT PROTEIN A, Host Pathogen Interactions, Clinical Application, Pulmonary Surfactant, Alveolar Macrophage, and Host Defense
While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular... more
While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular traps, where they play an important role in NET-mediated antimicrobial killing. Here, we show anti-influenza activity of histones against both seasonal H3N2 and H1N1, but not pandemic H1N1. The arginine rich histones, H3 and H4, had greater neutralizing and viral aggregating activity than the lysine rich histones, H2A and H2B. Of all core histones, histone H4 is most potent in neutralizing IAV, and incubation with IAV with histone H4 results in a decrease in uptake and viral replication by epithelial cells when measured by qRT-PCR. The antiviral activity of histone H4 is mediated principally by direct effects on viral particles. Histone H4 binds to IAV as assessed by ELISA and co-sedimentation of H4 with IAV. H4 also induces aggregation, as assessed by ...
Research Interests:
Influenza is a major burden to public health. Due to high mutation rates and selection pressure, mutant viruses emerge which are resistant to currently used antiviral drugs. Therefore, there is a need for the development of novel classes... more
Influenza is a major burden to public health. Due to high mutation rates and selection pressure, mutant viruses emerge which are resistant to currently used antiviral drugs. Therefore, there is a need for the development of novel classes of antiviral drugs that suffer less from the emergence of resistant viruses. Antiviral drugs based on collectin-like surfactant protein D (SP-D) may fulfil these requirements. Especially porcine SP-D displays strong antiviral activity to influenza A viruses. In the present study the antiviral activity of recombinant porcine SP-D was investigated in ex vivo cultures of respiratory tract tissue infected with human influenza A virus of the H3N2 subtype. Porcine SP-D has antiviral activity in these test systems. It is suggested that porcine SP-D may be used as a venue to develop a novel class of antiviral drugs.
Research Interests:
Research Interests: Biological Sciences, Humans, Virus, Animals, Lectins, and 4 moreGlycosylation, Swine, Protein Binding, and Collectins
Research Interests:
Research Interests: Multidisciplinary, Higher Order Thinking, Seasonality, Cell line, Humans, and 15 moreinfluenza A, Text, Animals, PLoS one, Neuraminidase, Epithelial cells, Trachea, influenza A virus, SURFACTANT PROTEIN D, Ferrets, Antiviral Activity, Recombinant Proteins, Sus Scrofa, Innate Immune System, and Upper respiratory tract
Research Interests:
Research Interests:
Research Interests:
Infection with gram-positive bacteria is a major cause of pneumonia. Surfactant proteins A (SP-A) and D (SP-D) are thought to play an important role in the innate immunity of the lung. Both proteins can bind to gram-positive bacteria.... more
Infection with gram-positive bacteria is a major cause of pneumonia. Surfactant proteins A (SP-A) and D (SP-D) are thought to play an important role in the innate immunity of the lung. Both proteins can bind to gram-positive bacteria. Until now, it was not known with which surface component(s) of gram-positive bacteria SP-A and SP-D interact. Lipoteichoic acid (LTA) and peptidoglycan (PepG) are components of the cell wall of gram-positive bacteria. By use of a solid phase-based binding assay, LTA of Bacillus subtilis was shown to be bound by SP-D but not by SP-A. Unmodified PepG of Staphylococcus aureus was bound by SP-D. SP-D binding to both LTA and PepG was calcium dependent and carbohydrate inhibitable. These results indicate that SP-D interacts with gram-positive bacteria via binding to the cell wall components LTA and PepG and that the carbohydrate recognition domain is responsible for this binding.