The polysaccharide capsule of Streptococcus pneumonia partially impedes MyD88-mediated immunity during pneumonia in mice.

Alex F De Vos,Onno J De Boer,Regina De Beer,Peter W Hermans,Cornelis Van ‘T Veer,Alexander P N A De Porto,Tom Van Der Poll,Adriana J J Lammers,Mark C Dessing,Sandrine Florquin,Sanne Terpstra,Hester J Bootsma

doi:10.1371/journal.pone.0118181

Alex F De Vos, Onno J De Boer + Show 10 more

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https://doi.org/10.1371/journal.pone.0118181

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Abstract

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 serotype 2 S. pneumoniae D39 or with an isogenic capsule locus deletion mutant (D39∆cps), 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 D39∆cps, 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.

Highlights

Analysis of bacterial outgrowth in the lung showed that Myd88-/- mice had a strongly diminished capacity to clear D39Δcps: whereas Wild type (WT) mice demonstrated a >105-fold reduction in pulmonary bacterial loads between 6 and 24 hours after infection, the reduction in Myd88-/- mice was only ~102-fold in this time frame
Since Toll-like receptors (TLR) ligands are masked by capsular polysaccharides in certain bacteria [30,31], we here studied the role of the pneumococcal capsule in myeloid differentiation primary-response protein 88 (MyD88)-mediated antibacterial defense against S. pneumoniae using the serotype 2 strain D39 and D39Δcps
While the present finding of enhanced bacterial growth of D39 in Myd88-/- mice is in accordance with earlier results after infection with serotype 4 or 19F S. pneumoniae [18], we demonstrate that MyD88 plays a more important role in limiting pneumococcal growth after infection with D39Δcps

Summary

Introduction

The interaction between pneumolysin and TLR4 has been found to limit the growth of pneumococci in the nasopharynx in a model of colonization [14,15] whereas TLR4 may contribute to antibacterial defense during pneumococcal infection of the lower airways [16]. In accordance with a role for TLR signaling in host defense against pneumococcal pneumonia, MyD88 deficient (Myd88-/-) mice were reported to show a profoundly enhanced growth of pneumococci and a strongly reduced survival after intranasal infection with serotype 4 or 19F S. pneumoniae strains [18]. The capsule potentially interferes with innate immune responses by masking several TLR ligands associated with the pneumococcal cell wall, including lipoteichoic acid and lipopeptides [3,19]. Our findings reveal that the polysaccharide capsule partially protects pneumococci against MyD88-mediated immunity during pneumonia in mice

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