B. pertussis interfere with the host inflammatory response

HUGO A. VALDEZ; JUAN MARCOS OVIEDO; JIMENA ALVAREZ HAYES; RODRÍGUEZ, MARIA E

Buenos Aires

Congreso; LASID-SAI-FAIC meeting; 2015

LASID-SAI-FAIC

Our laboratory recently demonstrated that B.pertussis (Bp) has the ability to manipulate the host transcriptional defense response eventually enabling its own survival and replication inside macrophages. In this work we examined the inflammatory response THP1 cells during the Bp infection at 3, 24 and 48 h. qRT-PCR results showed that, 3 hours after wild type Bp infection, IL-10 and SOCS3 were highly up-regulated and TNF-α moderately up-regulated while SOCS1 expression was not significantly modified. 48 hours, after infection SOCS1 expression level was significantly up-regulated while TNF-α and SOCS3 were strongly down modulated and IL-10 remained inchanged. The changes inflammatory cytoquines were further confirmed at protein levels by ELISA. Infections assays ran in parallel with Bp mutants deficient in the production of Ptx and CyaA, we found that CyaA is partially involved in the early up-regulation of the expression of IL-10 and SOCS3, and that both toxins are involved in the increase of SOCS1 at 48 h. These results are particularly interesting because a high SOCS1/SOCS3 expression ratio is characteristic of M2 macrophage phenotype, permissive for intracellular survival of bacterial pathogens. Accordingly, by mean of polymixin B protection assays we observed that any of the toxin defective mutants had a significantly lower intracellular survival 48 hours after infection as compared with the wild type strain. These results suggest that B. pertussis is able to manipulate the inflammatory response of the host cell through its two main toxins eventually creating a permissive intracellular environment.