Stimulated innate resistance event (StIR) in Bordetella pertussis infection is dependent on reactive oxygen species production.

ZURITA EUGENIA; GRISELDA MORENO; ERREA AGUSTINA; ORMAZABAL MAXIMILIAN; MARTIN RUMBO; DANIELA HOZBOR

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2013

0019-9567

The exacerbated induction of innate immune response in airways can abrogate diverse lung 16 infections by a phenomenon known as stimulated innate resistance (StIR). We have 17 recently demonstrated that the enhancement of innate response activation can efficiently 18 impair Bordetella pertussis colonization in a TLR4-dependent manner. The aim of this 19 work was to further characterize the effect of LPS in StIR and to identify the mechanisms 20 that mediate this process. Our results showed that bacterial infection was completely 21 abrogated in treated mice when the LPS of B. pertussis (1 µg) was added before (48 h or 24 h), after (24 h) or simultaneously with the B. pertussis challenge (107 22 CFU). Moreover, we 23 detected that LPS completely cleared bacterial infection as soon as 2 h post-treatment. This 24 timing suggests that the observed StIR phenomenon should be mediated by fast-acting 25 antimicrobial mechanisms. Although neutrophil recruitment was already evident at this 26 time point, depletion assays using an anti-GR-1 antibody showed that B. pertussis clearance 27 is achieved even in the absence of neutrophils. To evaluate the possible role of free radicals 28 in the StIR, we performed animal assays using the antioxidant N-acetyl cysteine (NAC), 29 which is known to inactivate oxidant species. NAC administration blocked the B. pertussis 30 clearance induced by LPS. Nitrite concentrations were also increased in the LPS-treated 31 mice; however, the inhibition of nitric oxide synthetases did not suppress the LPS-induced 32 bacterial clearance. Taken together, our results showed that ROS play an essential role in 33 the TLR4-dependent innate clearance of B. pertussis.