Melanie Hamon, France
Institut Pasteur Cell biology and InfectionAuthor Of 1 Presentation
PNEUMOCOCCAL SEROTYPE 6B REQUIRES KDM6B, A HISTONE DEMETHYLASE, FOR ASYMPTOMATIC INFECTION (ID 205)
Abstract
Background
Streptococcus pneumoniae is a natural colonizer of the human respiratory tract, and a global priority pathogen comprised of over 90 different serotypes. Respiratory epithelial cells are among the first to encounter the organism, however, their role in orchestrating the response to infection is unknown.
Methods
We compared epithelial cell responses to serotype 4 (Tigr4), causing lethal symptomatic infection in mice, to a serotype 6B, which induces asymptomatic infection even at high inoculum.
Results
We found these interactions lead to divergent responses in either asymptomatic, host-limiting infection, or symptomatic, invasive pneumococcal infection. Our data show that 6B induces a distinct inflammatory profile in comparison to Tigr4, which requires KDM6B, a eukaryotic histone demethylase, and the cytokine IL-11. At the molecular level, we reveal that KDM6B demethylation of histone H3 remodels the promoter of IL-11 for expression. Finally, through chemical inhibition of KDM6B enzymatic activity, or exogenous addition of IL-11, the asymptomatic and symptomatic host response to pneumococcus can be interchanged.
Conclusions
Thus, we show for the first time that asymptomatic infection is driving a host response dependent on KDM6B and IL-11, and these factors are critical in modulating a divergent response to different pneumococcal serotypes.
Presenter of 1 Presentation
PNEUMOCOCCAL SEROTYPE 6B REQUIRES KDM6B, A HISTONE DEMETHYLASE, FOR ASYMPTOMATIC INFECTION (ID 205)
Abstract
Background
Streptococcus pneumoniae is a natural colonizer of the human respiratory tract, and a global priority pathogen comprised of over 90 different serotypes. Respiratory epithelial cells are among the first to encounter the organism, however, their role in orchestrating the response to infection is unknown.
Methods
We compared epithelial cell responses to serotype 4 (Tigr4), causing lethal symptomatic infection in mice, to a serotype 6B, which induces asymptomatic infection even at high inoculum.
Results
We found these interactions lead to divergent responses in either asymptomatic, host-limiting infection, or symptomatic, invasive pneumococcal infection. Our data show that 6B induces a distinct inflammatory profile in comparison to Tigr4, which requires KDM6B, a eukaryotic histone demethylase, and the cytokine IL-11. At the molecular level, we reveal that KDM6B demethylation of histone H3 remodels the promoter of IL-11 for expression. Finally, through chemical inhibition of KDM6B enzymatic activity, or exogenous addition of IL-11, the asymptomatic and symptomatic host response to pneumococcus can be interchanged.
Conclusions
Thus, we show for the first time that asymptomatic infection is driving a host response dependent on KDM6B and IL-11, and these factors are critical in modulating a divergent response to different pneumococcal serotypes.