TY - JOUR
T1 - The polysaccharide capsule of streptococcus pneumonia partially impedes myd88- Mediated immunity during pneumonia in mice
AU - De Vos, Alex F.
AU - Dessing, Mark C.
AU - Lammers, Adriana J.J.
AU - De Porto, Alexander P.N.A.
AU - Florquin, Sandrine
AU - De Boer, Onno J.
AU - De Beer, Regina
AU - Terpstra, Sanne
AU - Bootsma, Hester J.
AU - Hermans, Peter W.
AU - Van Veer, Cornelis T.
AU - Van Poll, Tom Der
AU - van 't Veer, Cornelis
PY - 2015/2/20
Y1 - 2015/2/20
N2 - Toll-like receptors (TLR) and the downstream adaptor protein MyD88 are considered crucial for protective immunity during bacterial infections. Streptococcus (S.) pneumoniae is a human respiratory pathogen and a large majority of clinical pneumococcal isolates expresses an external polysaccharide capsule. We here sought to determine the role of pneumococcal capsule in MyD88-mediated antibacterial defense during S. pneumonia pneumonia. Wild type (WT) and Myd88-/- mice were inoculated intranasally with serotype2 S. pneumoniae D39 or with an isogenic capsule locus deletion mutant (D39Äcps), and analysed for bacterial outgrowth and inflammatory responses in the lung. As compared to WT mice, Myd88-/- mice infected with D39 demonstrated a modestly impaired bacterial clearance accompanied by decreased inflammatory responses in the lung. Strikingly, while WT mice rapidly cleared D39Äcps, Myd88-/- mice showed 105-fold higher bacterial burdens in their lungs and dissemination to blood 24 hours after infection. These data suggest that the pneumococcal capsule impairs recognition of TLR ligands expressed by S. pneumoniae and thereby partially impedes MyD88-mediated antibacterial defense.
AB - Toll-like receptors (TLR) and the downstream adaptor protein MyD88 are considered crucial for protective immunity during bacterial infections. Streptococcus (S.) pneumoniae is a human respiratory pathogen and a large majority of clinical pneumococcal isolates expresses an external polysaccharide capsule. We here sought to determine the role of pneumococcal capsule in MyD88-mediated antibacterial defense during S. pneumonia pneumonia. Wild type (WT) and Myd88-/- mice were inoculated intranasally with serotype2 S. pneumoniae D39 or with an isogenic capsule locus deletion mutant (D39Äcps), and analysed for bacterial outgrowth and inflammatory responses in the lung. As compared to WT mice, Myd88-/- mice infected with D39 demonstrated a modestly impaired bacterial clearance accompanied by decreased inflammatory responses in the lung. Strikingly, while WT mice rapidly cleared D39Äcps, Myd88-/- mice showed 105-fold higher bacterial burdens in their lungs and dissemination to blood 24 hours after infection. These data suggest that the pneumococcal capsule impairs recognition of TLR ligands expressed by S. pneumoniae and thereby partially impedes MyD88-mediated antibacterial defense.
UR - http://www.scopus.com/inward/record.url?scp=84923677298&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pone.0118181
DO - https://doi.org/10.1371/journal.pone.0118181
M3 - Article
C2 - 25700108
SN - 1932-6203
VL - 10
SP - e0118181
JO - PLOS ONE
JF - PLOS ONE
IS - 2
M1 - e0118181
ER -