Aeromonas hydrophila leads to both intestinal and extraintestinal
infections in animals and humans, and the underlying mechanisms leading to mortality are largely unknown. By using a septicemic mouse model of
infection, we showed that animals challenged with A. hydrophila die because of kidney and liver damage,
hypoglycemia, and
thrombocytopenia. Pretreatment of animals with quorum-sensing-associated signaling molecules N-
acyl homoserine lactones (AHLs), such as butanoyl and hexanoyl
homoserine lactones (C(4)- and C(6)-HSLs), as well as N-3-oxododecanoyl (3-oxo-C(12))-HSL, prevented clinical sequelae, resulting in increased survivability of mice. Since little is known as to how different AHLs modulate the immune response during
infection, we treated mice with the above AHLs prior to lethal A. hydrophila
infection. When we compared results in such animals to those in controls, the treated animals exhibited a significantly reduced bacterial load in the blood and other mouse organs, as well as various levels of
cytokines/
chemokines. Importantly, neutrophil numbers were significantly elevated in the blood of C(6)-HSL-treated mice compared to those in animals given
phosphate-buffered saline and then infected with the bacteria. These findings coincided with the fact that neutropenic animals were more susceptible to A. hydrophila
infection than normal mice. Our data suggested that neutrophils quickly cleared bacteria by either phagocytosis or possibly another mechanism(s) during
infection. In a parallel study, we indeed showed that other predominant immune cells inflicted during A. hydrophila
infections, such as murine macrophages, when they were pretreated with AHLs, rapidly phagocytosed bacteria, whereas untreated cells phagocytosed fewer bacteria. This study is the first to report that AHL pretreatment modulates the innate immune response in mice and enhances their survivability during A. hydrophila
infection.