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Molecular Pathogenesis

Nontypeable Haemophilus influenzae Invasive Blood Isolates Are Mainly Phosphorylcholine Negative and Show Decreased Complement-Mediated Killing That Is Associated with Lower Binding of IgM and CRP in Comparison to Colonizing Isolates from the Oropharynx

Jeroen D. Langereis, Amelieke J. H. Cremers, Marloes Vissers, Josine van Beek, Jacques F. Meis, Marien I. de Jonge
Shelley M. Payne, Editor
Jeroen D. Langereis
Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, the NetherlandsRadboud Center for Infectious Diseases, Radboudumc, Nijmegen, the Netherlands
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  • ORCID record for Jeroen D. Langereis
Amelieke J. H. Cremers
Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, the NetherlandsDepartment of Medical Microbiology, Radboudumc, Nijmegen, the Netherlands
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Marloes Vissers
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
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Josine van Beek
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
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Jacques F. Meis
Department of Medical Microbiology, Radboudumc, Nijmegen, the NetherlandsDepartment of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
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Marien I. de Jonge
Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, the NetherlandsRadboud Center for Infectious Diseases, Radboudumc, Nijmegen, the Netherlands
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Shelley M. Payne
The University of Texas at Austin
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DOI: 10.1128/IAI.00604-18
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ABSTRACT

Nontypeable Haemophilus influenzae (NTHi) bacteria express various molecules that contribute to their virulence. The presence of phosphocholine (PCho) on NTHi lipooligosaccharide increases adhesion to epithelial cells and is an advantage for the bacterium, enabling nasopharyngeal colonization, as measured in humans and animal models. However, when PCho is expressed on the lipooligosaccharide, it is also recognized by the acute-phase protein C-reactive protein (CRP) and PCho-specific antibodies, both of which are potent initiators of the classical pathway of complement activation. In this study, we show that blood isolates, which are exposed to CRP and PCho-specific antibodies in the bloodstream, have a higher survival in serum than oropharyngeal isolates, which was associated with a decreased presence of PCho. PCholow strains showed decreased IgM, CRP, and complement C3 deposition, which was associated with increased survival in human serum. Consistent with the case for the PCholow strains, removal of PCho expression by licA gene deletion decreased IgM, CRP, and complement C3 deposition, which increased survival in human serum. Complement-mediated killing of PChohigh strains was mainly dependent on binding of IgM to the bacterial surface. These data support the hypothesis that a PCholow phenotype was selected in blood during invasive disease, which increased resistance to serum killing, mainly due to lowered IgM and CRP binding to the bacterial surface.

FOOTNOTES

    • Received 6 August 2018.
    • Returned for modification 11 September 2018.
    • Accepted 9 November 2018.
    • Accepted manuscript posted online 19 November 2018.
  • Supplemental material for this article may be found at https://doi.org/10.1128/IAI.00604-18.

  • Copyright © 2019 American Society for Microbiology.

All Rights Reserved.

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Nontypeable Haemophilus influenzae Invasive Blood Isolates Are Mainly Phosphorylcholine Negative and Show Decreased Complement-Mediated Killing That Is Associated with Lower Binding of IgM and CRP in Comparison to Colonizing Isolates from the Oropharynx
Jeroen D. Langereis, Amelieke J. H. Cremers, Marloes Vissers, Josine van Beek, Jacques F. Meis, Marien I. de Jonge
Infection and Immunity Jan 2019, 87 (2) e00604-18; DOI: 10.1128/IAI.00604-18

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Nontypeable Haemophilus influenzae Invasive Blood Isolates Are Mainly Phosphorylcholine Negative and Show Decreased Complement-Mediated Killing That Is Associated with Lower Binding of IgM and CRP in Comparison to Colonizing Isolates from the Oropharynx
Jeroen D. Langereis, Amelieke J. H. Cremers, Marloes Vissers, Josine van Beek, Jacques F. Meis, Marien I. de Jonge
Infection and Immunity Jan 2019, 87 (2) e00604-18; DOI: 10.1128/IAI.00604-18
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KEYWORDS

CRP
complement resistance
Haemophilus influenzae
IgM
lipooligosaccharide
phosphorylcholine
TEPC-15

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