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.
Highlights
Streptococcus pneumoniae is both a frequent colonizer of the human nasopharynx and a major cause of invasive diseases
Mice lacking inflammasome components or receptors for IL-1 or IL-18 show an altered susceptibility towards S. pneumoniae [23,24,25,26,29,30], indicating that inflammasomes are critical components of the innate defence system during pneumococcal infection
S. pneumoniae serotypes with variable haemolytic activities differentially stimulate caspase1-dependent production of IL-1β by human cells
Summary
Streptococcus pneumoniae is both a frequent colonizer of the human nasopharynx and a major cause of invasive diseases. Depending on preceding viral infections, the immune status of the host, and on the pneumococcal strain, an asymptomatic colonization can establish and progress to pneumonia, sepsis, or meningitis [1,2]. These infections are associated with high morbidity and mortality. Serotypes 3, 6B, 9N and others are associated with nasopharyngeal colonization and with infections in patients with underlying diseases, and with higher mortality when causing pneumonia. While the degree of encapsulation positively associates with colonization prevalence and virulence [5], other bacterial factors that affect the interaction with the hosts innate immune system might play a role
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