Intracellular b. pertussis modulates human macrophage defense gene expression

VALDEZ, HUGO; OVIEDO, JUAN MARCOS; GORGOJO, JUAN PABLO; RODRIGUEZ, MARÍA EUGENIA

Buenos Aires

Simposio; 11th International Bordetella Symposium; 2016

Bordetella Scientific Committee

The results showed that early transcriptional response to this pathogen was dominated by an up-regulation of host defense genes characteristics of macrophage activation like LYZ (lysozyme), CTSA (cathepsin), CTSC, CTSB, CTSD,CTSG, CTSS, CAT (catalase), IL-10, IL-8, TNF-α and SOCS3 (suppressor of cytokine signaling). At later time points both the bactericidal and the inflammatory response were progressively down-regulated and 48 hours after infection SOCS1 expression level was significantly up-regulated while TNF-α and SOCS3 were strongly down modulated. Infections assays ran in parallel with Bp mutants deficient in the production of Ptx and CyaA showed that Ptx is involved in the regulation of the expression of most of the genes implicated in the microbicidal activity that were down-modulated in infected cells, while the down-regulation of some others, as those involved in the inflammatory response, depends on the expression of either CyaA or Ptx. In agreement with these results both toxin defective mutants showed a significantly lower intracellular survival 48 hours after infection as compared with the wild type strain.