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Published on: January 17, 2014
Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue
Diana Fatykhova1, Anne Rabes1, Christoph Machnik1
1Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Abstract:
Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae, which can be sensed by the NLRP3 inflammasome. Among the over 90 serotypes, serotype 1 pneumococci (particularly MLST306) have emerged across the globe as a major cause of invasive disease. The cause for its particularity is, however, incompletely understood. We therefore examined pneumococcal infection in human cells and a human lung organ culture system mimicking infection of the lower respiratory tract. We demonstrate that different pneumococcal serotypes differentially activate inflammasome-dependent IL-1β production in human lung tissue and cells. Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype 1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1β production. Accordingly, purified haemolytic pneumolysin but not serotype 1-associated non-haemolytic toxin activates strong IL-1β production in human lungs. Our data suggest that the evasion of inflammasome-dependent innate immune responses by serotype 1 pneumococci might contribute to their ability to cause invasive diseases in humans.
Insights
Streptococcus pneumoniae serotype 1 evades immune detection by producing a non-haemolytic toxin, unlike other serotypes. This evasion mechanism may explain why serotype 1 causes severe invasive diseases like pneumonia and meningitis.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Streptococcus pneumoniae causes pneumonia, sepsis, and meningitis.
- Pneumolysin, a toxin from S. pneumoniae, is sensed by the NLRP3 inflammasome.
- Serotype 1 strains (MLST306) are increasingly linked to invasive pneumococcal disease.
Purpose of the Study:
- To investigate why S. pneumoniae serotype 1 causes significant invasive disease.
- To compare inflammasome activation by different pneumococcal serotypes.
- To elucidate the role of pneumolysin variants in immune evasion.
Main Methods:
- Infection of human lung cells and organ cultures.
- Measurement of inflammasome-dependent IL-1β production.
- Analysis of pneumolysin activity from different serotypes.
Main Results:
- Different S. pneumoniae serotypes differentially activate inflammasome-dependent IL-1β production.
- Serotypes 2, 3, 6B, and 9N with haemolytic pneumolysins strongly activate NLRP3 inflammasome.
- Serotype 1 and 8 strains with non-haemolytic toxins are poor activators of IL-1β.
- Purified haemolytic pneumolysin, but not serotype 1's toxin, strongly activates IL-1β in human lungs.
Conclusions:
- Serotype 1 pneumococci's non-haemolytic toxin may evade inflammasome-dependent innate immunity.
- This immune evasion could contribute to the high incidence of invasive disease caused by serotype 1.
- Understanding pneumolysin's role is crucial for combating invasive pneumococcal infections.
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