B. pertussis interfere with the host inflammatory response

VALDEZ, HUGO; OVIEDO, JUAN MARCOS; ALVAREZ HAYES, JIMENA; RODRIGUEZ, MARÍA EUGENIA

Buenos Aires

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Inmunología; 2015

Our laboratory recently demonstrated that B.pertussis(Bp) has the ability to manipulate the host transcriptional defenseresponse eventually enabling its own survival and replicationinside macrophages. In this work we examined the inflammatoryresponse THP1 cells during the Bp infection at 3, 24 and 48 h.qRT-PCR results showed that, 3 hours after wild type Bpinfection, IL-10 and SOCS3 were highly up-regulated and TNF-αmoderately up-regulated while SOCS1 expression was notsignificantly modified. 48 hours, after infection SOCS1 expressionlevel was significantly up-regulated while TNF-α and SOCS3were strongly down modulated and IL-10 remained inchanged.The changes inflammatory cytoquines were further confirmed atprotein levels by ELISA. Infections assays ran in parallel with Bpmutants deficient in the production of Ptx and CyaA, we foundthat CyaA is partially involved in the early up-regulation of theexpression of IL-10 and SOCS3, and that both toxins are involvedin the increase of SOCS1 at 48 h. These results are particularlyinteresting because a high SOCS1/SOCS3 expression ratio ischaracteristic of M2 macrophage phenotype, permissive forintracellular survival of bacterial pathogens. Accordingly, bymean of polymixin B protection assays we observed that any ofthe toxin defective mutants had a significantly lower intracellularsurvival 48 hours after infection as compared with the wild typestrain. These results suggest that B. pertussis is able to manipulatethe inflammatory response of the host cell through its two maintoxins eventually creating a permissive intracellular environment.