Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue

PloS One
Diana FatykhovaBastian Opitz

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 ...Continue Reading

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Mar 18, 2016·The Journal of Infectious Diseases·Kathrin GrissBernd Schmeck
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Jan 12, 2021·Frontiers in Immunology·Surabhi SurabhiNikolai Siemens
May 14, 2021·Frontiers in Immunology·Florencia FerraraJosé Alejandro Chabalgoity

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Methods Mentioned

BETA
PCR
affinity purification
Assay
ELISA

Software Mentioned

MODELLER
GenDB
r2cat
Prism
GraphPad
SPades

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