The effect of pertussis toxin on the innate immune response to Bordetella pertussis infection in mice
AdvisorCarbonetti, Nicholas H.
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AbstractBordetella pertussis is a small Gram-negative bacterium that infects the human respiratory tract and causes the disease pertussis, also known as whooping cough. B. pertussis binds to ciliated cells in the trachea and proliferates within the upper and lower respiratory tract, where several toxins are released. Pertussis toxin (PT), produced exclusively by B. pertussis, and adenylate cyclase toxin (ACT) are important virulence factors of B. pertussis; however, their complete role during infection is not yet clear. Our studies showed that PT inhibits early neutrophil recruitment to the lung tissue (d1) and airways (d1-2) in response to infection with 5x105 CFU of B. pertussis by inhibiting the early production of neutrophil-attracting chemokines (6 hrs). However, at the peak of infection, a strong inflammatory Th1/Th17 response is produced, in part by PT and ACT activity. The production of IL-17 results in the induction of chemokine production as well as a neutrophil recruitment to the airways. Neutrophil depletion experiments suggested that neutrophils are not important in response to B. pertussis in naive mice. However, in an immune mouse model, neutrophils played a role in controlling the infection. Furthermore, in contrast to findings in naive mice, neutrophils appear to be the main target for ACT activity in immune mice, suggesting that B. pertussis may have evolved to evade immune responses in previously infected (or vaccinated) individuals.
DescriptionUniversity of Maryland, Baltimore. Microbiology. Ph.D. 2008
Health Sciences, Immunology
Virulence Factors, Bordetella