Bordetella pertussis naturally occurring isolates with altered lipooligosaccharide structure fail to fully mature human dendritic cells.

Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Despite high vaccination coverage, outbreaks are being increasingly reported worldwide. Possible explanations include adaptation of this pathogen, which may interfere with recognition by the innate immune system. Here, we describe innate immune recognition and responses to different B. pertussis clinical isolates. By using HEK-Blue cells transfected with different pattern recognition receptors, we found that 3 out of 19 clinical isolates fail to activate TLR4. These findings were confirmed using the monocytic MM6 cell line. Although incubation with high concentrations of these 3 strains resulted in significant activation of the MM6 cells, it was found to occur mainly through interaction with TLR2 and not through TLR4. When using live bacteria, these 3 strains also failed to activate TLR4 on HEK-Blue cells and activation of MM6 cells or human monocyte-derived dendritic cells was significantly less compared to activation with the other 16 strains. Mass spectrum analysis of the lipid A from these 3 strains indicated an altered structure of this molecule. Gene sequence analysis revealed mutations in genes involved in lipid A synthesis. Findings from this study indicate that B. pertussis isolates, that do not activate TLR4, occur naturally and that this phenotype may give this bacterium an advantage in tempering the innate immune response and establishing infection. Knowledge on the strategies used by this pathogen on evading the host immune response is essential for the improvement of current vaccines or for the development of new ones


Authors:Brummelman J1, Veerman R1, Hamstra HJ1, Deuss AJ1, Schuijt TJ1, Sloots A2, Kuipers B1, van Els CA1, van der Ley P2, Mooi FR1, Han WG1, Pinelli E3.

Journal:Infect Immun. 2014