1887

Abstract

Quorum-sensing systems have been reported to play a critical role in the pathogenesis of several bacterial infections. Recent data have demonstrated that -3-oxododecanoyl--homoserine lactone (3-oxo-C-homoserine lactone, 3-oxo-C-HSL), but not -butanoyl--homoserine lactone (C-HSL), induces apoptosis in macrophages and neutrophils. In the present study, the effects of active immunization with 3-oxo-C-HSL–carrier protein conjugate on acute lung infection in mice were investigated. Immunization with 3-oxo-C-HSL–BSA conjugate (subcutaneous, four times, at 2-week intervals) elaborated significant amounts of specific antibody in serum. Control and immunized mice were intranasally challenged with approximately 3×10 c.f.u. PAO1, and survival was then compared. All control mice died by day 2 post bacterial challenge, while 36 % of immunized mice survived to day 4 (<0.05). Interestingly, bacterial numbers in the lungs did not differ between control and immunized groups, whereas the levels of pulmonary tumour necrosis factor (TNF)- in the immunized mice were significantly lower than those of control mice (<0.05). Furthermore, the extractable 3-oxo-C-HSL levels in serum and lung homogenate were also significantly diminished in the immunized mice. Immune serum completely rescued reduction of cell viability by 3-oxo-C-HSL-mediated apoptosis in macrophages . These results demonstrated that specific antibody to 3-oxo-C-HSL plays a protective role in acute infection, probably through blocking of host inflammatory responses, without altering lung bacterial burden. The present data identify a promising potential vaccine strategy targeting bacterial quorum-sensing molecules, including autoinducers.

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2006-10-01
2020-07-04
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