Pertussis toxin inhibits neutrophil recruitment to delay antibody-mediated clearance of Bordetella pertussis

J Clin Invest. 2005 Dec;115(12):3594-601. doi: 10.1172/JCI24609. Epub 2005 Nov 17.

Abstract

Whooping cough is considered a childhood disease, although there is growing evidence that children are infected by adult carriers. Additionally, increasing numbers of vaccinated adults are being diagnosed with Bordetella pertussis disease. Thus it is critical to understand how B. pertussis remains endemic even in highly vaccinated or immune populations. Here we used the mouse model to examine the nature of sterilizing immunity to B. pertussis. Antibodies were necessary to control infection but did not rapidly clear B. pertussis from the lungs. However, antibodies affected B. pertussis after a delay of at least a week by a mechanism that involved neutrophils and Fc receptors, suggesting that neutrophils phagocytose and clear antibody-opsonized bacteria via Fc receptors. B. pertussis blocked migration of neutrophils and inhibited their recruitment to the lungs during the first week of infection by a pertussis toxin-dependent (PTx-dependent) mechanism; a PTx mutant of B. pertussis induced rapid neutrophil recruitment and was rapidly cleared from the lungs by adoptively transferred antibodies. Depletion of neutrophils abrogated the defects of the PTx mutant. Together these results indicate that PTx inhibits neutrophil recruitment, which consequently allows B. pertussis to avoid rapid antibody-mediated clearance and therefore successfully infect immune hosts.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Bacterial / chemistry
  • Aorta / cytology
  • Bordetella Infections / metabolism
  • Bordetella pertussis / metabolism*
  • Cell Movement
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Endothelium, Vascular / cytology
  • Humans
  • Leukocytes / cytology
  • Leukocytes / microbiology
  • Lung / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Neutrophils / microbiology*
  • Pertussis Toxin / metabolism
  • Pertussis Toxin / pharmacology*
  • Phagocytosis
  • Receptors, Fc / metabolism
  • Receptors, IgG / metabolism
  • Time Factors
  • Virulence Factors, Bordetella / metabolism
  • Whooping Cough / microbiology
  • Whooping Cough / therapy

Substances

  • Antigens, Bacterial
  • Chemokines
  • Cytokines
  • Receptors, Fc
  • Receptors, IgG
  • Virulence Factors, Bordetella
  • Pertussis Toxin