Bordetella pertussis modulates human macrophage defense gene expression

VALDEZ, HUGO; LAMBERTI, YANINA; OVIEDO, JUAN MARCOS; RODRIGUEZ, MARIA EUGENIA; GORGOJO, JUAN

Pathogens and disease

Oxford University press/FEMS

Año: 2016 vol. 74 p. 1 - 14

2049-632X

Bordetella pertussis, the etiological agent of whooping cough, still causes outbreaks. We recently found evidence that B.pertussis can survive and even replicate inside human macrophages, indicating that this host cell might serve as a niche forpersistence. In this work, we examined the interaction of B. pertussis with a human monocyte cell line (THP-1) thatdifferentiates into macrophages in culture in order to investigate the host cell response to the infection and themechanisms that promote that intracellular survival. To that end, we investigated the expression profile of a selectednumber of genes involved in cellular bactericidal activity and the inflammatory response during the early and late phasesof infection. The bactericidal and inflammatory response of infected macrophages was progressively downregulated, whilethe number of THP-1 cells heavily loaded with live bacteria increased over time postinfection. Two of the main toxins of B.pertussis, pertussis toxin (Ptx) and adenylate cyclase (CyaA), were found to be involved in manipulating the host cellresponse. Therefore, failure to express either toxin proved detrimental to the development of intracellular infections bythose bacteria. Taken together, these results support the relevance of host defense gene manipulation to the outcome ofthe interaction between B. pertussis and macrophages.