Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells

• DOI: 10.1128/iai.02197-14
• Publication Date: 2014-10-28T05:04:39Z
• Authors: Jolanda Brummelman; Rosanne E. Veerman; Hendrik Jan Hamstra; Anna J. M. Deuss; Tim J. Schuijt; Arjen Sloots; Betsy Kuipers; Cécile A. C. M. v...; Peter van der Ley; Frits R. Mooi; Wanda G. H. Han; Elena Pinelli
• Keywords: Pertactin; Pathogen-associated molecular pattern

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 this pathogen, which may interfere with recognition by innate immune system. Here, we describe responses to different B. clinical isolates. By using HEK-Blue cells transfected pattern receptors, found that 3 out 19 isolates failed activate Toll-like receptor 4 (TLR4). These findings were confirmed monocytic MM6 cell line. Although incubation concentrations these strains resulted in significant activation cells, it was occur mainly through interaction TLR2 not TLR4. When live bacteria, also TLR4 on or human monocyte-derived dendritic significantly lower than induced other 16 strains. Mass spectrum analysis lipid A moieties from indicated an altered structure molecule. Gene sequence revealed mutations genes involved synthesis. Findings study indicate do naturally phenotype give advantage tempering response establishing infection. Knowledge strategies used pathogen evading host essential for improvement current vaccines development new ones.