Inflammatory response suppression by Bordetella pertussis toxins.

VALDEZ, HUGO; OVIEDO, JUAN MARCOS; RODRÍGUEZ, MARÍA EUGENIA

Mar del Plata

Congreso; LXII Reunión Científica Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología

Whooping cough is a reemerging disease caused by Bordetella pertussis (Bp). Our laboratory recently demonstrated that Bp has the capacity to survive and replicate inside macrophages. Recently, numerous studies have reported that intracellular pathogens would have the ability to manipulate the host transcriptional response to achieve survival, but little is known about the effectors of this manipulation. Bp has many virulence factors and toxins and the most relevant are adenylate cyclase toxin (CyaA) and pertussis toxin (Ptx). To examine the role of these toxins during intracellular survival of Bp, we studied comparative infections caused by Bp wild type (wtBp), Bp lacking the expression of CyaA (BpΔCyaA), and Bp lacking the expression of PTx (BpΔPtx). We investigated the expression of host cell genes involved in the inflammatory response, such as TNF-α, IL-8 and NFK-β. Using THP1 cell model mRNA was recovery at 3-, 24- and 48 h after infection. Intracellular infection with wtBp caused a strong up-regulation of TNF-α, IL-8 and NFK-β at 3h post infection. The expression of the these genes showed a progressive down modulation in macrophages infected with wtBP from 3- to 48-h post-infection. The same down modulation was observed in macrophages infected with either mutant only in the case of NKF-β. Conversely, TNF-α expression was up-regulated 5- and 7-fold in BpΔCyaA and BpΔPTx infected cells, respectively, at 48-h post infection. Similarly, IL-8 expression was up-regulated 6-fold and 7-fold in BpΔCyaA and BpΔPTx infected cells, respectively, 48 hour post infection. The expression level of these cytoquines was confirmed by ELISA. These results suggest that B. pertussis is able to manipulate the inflammatory response of the host cell and that this ability is dependent on these two toxins. Importantly, intracellular survival studies showed a significant decrease in bacterial viability of either mutant. Taken together these results indicate that the ability of Bp to control the regulatory mechanisms of cytokine production might guarantee its permanence and persistence