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Molecular Pathogenesis

Antibody Binding and Complement-Mediated Killing of Invasive Haemophilus influenzae Isolates from Spain, Portugal, and the Netherlands

Elena Dudukina, Laura de Smit, Giel J. A. Verhagen, Arie van de Ende, José María Marimón, Paula Bajanca-Lavado, Carmen Ardanuy, Sara Marti, Marien I. de Jonge, Jeroen D. Langereis
Manuela Raffatellu, Editor
Elena Dudukina
aSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
bRadboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
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Laura de Smit
aSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
bRadboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
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Giel J. A. Verhagen
aSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
bRadboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
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Arie van de Ende
cAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention and the Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam, the Netherlands
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  • ORCID record for Arie van de Ende
José María Marimón
dBiodonostia, Infectious Diseases Area, Respiratory Infection and Antimicrobial Resistance Group, Osakidetza Basque Health Service, University Hospital Donostia, San Sebastian, Basque Country, Spain
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Paula Bajanca-Lavado
eDepartment of Infectious Disease, National Institute of Health, Lisbon, Portugal
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Carmen Ardanuy
fMicrobiology Department, Hospital Universitari de Bellvitge, Universitat de Barcelona-IDIBELL, Barcelona, Spain
gCentro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
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Sara Marti
fMicrobiology Department, Hospital Universitari de Bellvitge, Universitat de Barcelona-IDIBELL, Barcelona, Spain
gCentro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
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Marien I. de Jonge
aSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
bRadboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
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Jeroen D. Langereis
aSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
bRadboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
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Manuela Raffatellu
University of California San Diego School of Medicine
Roles: Editor
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DOI: 10.1128/IAI.00454-20
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ABSTRACT

Haemophilus influenzae is a Gram-negative bacterium that can be classified into typeable (types a through f) and nontypeable (NTHi) groups. This opportunistic pathogen asymptomatically colonizes the mucosal epithelium of the upper respiratory tract, from where it spreads to other neighboring regions, potentially leading to disease. Infection with NTHi can cause otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease, and pneumonia, but it is increasingly causing invasive disease, including bacteremia and meningitis. Invasive NTHi strains are more resistant to complement-mediated killing. However, the mechanisms of complement resistance have never been studied in large numbers of invasive NTHi strains. In this study, we determined the relationship between binding of IgG or IgM and the bacterial survival in normal human serum for 267 invasive H. influenzae strains from Spain, Portugal, and the Netherlands, of which the majority (200 [75%]) were NTHi. NTHi bacteria opsonized with high levels of IgM had the lowest survival in human serum. IgM binding to the bacterial surface, but not IgG binding, was shown to be associated with complement-mediated killing of NTHi strains. We conclude that evasion of IgM binding by NTHi strains increases survival in blood, thereby potentially contributing to their ability to cause severe invasive diseases.

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Antibody Binding and Complement-Mediated Killing of Invasive Haemophilus influenzae Isolates from Spain, Portugal, and the Netherlands
Elena Dudukina, Laura de Smit, Giel J. A. Verhagen, Arie van de Ende, José María Marimón, Paula Bajanca-Lavado, Carmen Ardanuy, Sara Marti, Marien I. de Jonge, Jeroen D. Langereis
Infection and Immunity Sep 2020, 88 (10) e00454-20; DOI: 10.1128/IAI.00454-20

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Antibody Binding and Complement-Mediated Killing of Invasive Haemophilus influenzae Isolates from Spain, Portugal, and the Netherlands
Elena Dudukina, Laura de Smit, Giel J. A. Verhagen, Arie van de Ende, José María Marimón, Paula Bajanca-Lavado, Carmen Ardanuy, Sara Marti, Marien I. de Jonge, Jeroen D. Langereis
Infection and Immunity Sep 2020, 88 (10) e00454-20; DOI: 10.1128/IAI.00454-20
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KEYWORDS

Haemophilus influenzae
IgG
IgM
complement evasion
sepsis
meningitis
bacteremia

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