INSTITUTO DE BIOTECNOLOGIA Y BIOLOGIA MOLECULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Stimulated innate resistance event (StIR) in Bordetella pertussis infection is dependent on reactive oxygen species production.
ZURITA E; MORENO G; ERREA A; ORMAZABAL M; CURCIARELLO R; RUMBO M; HOZBOR D
Congreso; 10 th International Symposium on Bordetella; 2013
Trinity Biomedical Science Institute
The exacerbated induction of innate immune response in airways can abrogate diverse lunginfections by a phenomenon known as stimulated innate resistance (StIR). We have demonstratedthat the enhancement of innate response activation can efficiently impair Bordetella pertussiscolonization in a TLR4-dependent manner. The aim of the present work was to further characterizethis phenomenon. Our results showed that bacterial infection was completely abrogated in treatedmice when the B. pertussis LPS (1μg) was added before (48h or 24h), after (24h) orsimultaneously with the B. pertussis challenge (107CFU). Moreover, we detected that LPScompletely cleared bacterial infection as soon as 2 h post-treatment. This timing suggests that StIRshould be mediated by fast-acting antimicrobial mechanisms. To evaluate the possible role of freeradicals in the StIR, we performed animal assays using the antioxidant N-acetyl cysteine (NAC).NAC administration blocked the B. pertussis clearance induced by LPS. Nitrite concentrations werealso increased in the LPS-treated mice; however, the inhibition of nitric oxide synthetases did notsuppress the LPS-induced bacterial clearance. In order to evaluate the role of epithelial cells in ROSproduction induced by LPS, we performed in vitro experiments using human alveolar epithelialA549. We observed that the exposure of A549 cells to LPS increased the production ofinflammatory cytokines and ROS levels. This induction is LPS concentration- and time-dependent.Taken together, our results showed that ROS induced at least in part by the host epithelial cellsplay an essential role in the TLR4-dependent innate clearance of B. pertussis.