Stimulation of gp91 Phagocytic Oxidase and Reactive Oxygen Species in Neutrophils by an Avirulent Salmonella enterica Serovar Infantis Strain Protects Gnotobiotic Piglets from Lethal Challenge with Serovar Typhimurium Strain F98 without Inducing Intestinal Pathology

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Abstract
Preinoculation of susceptible 5-day-old gnotobiotic piglets with Salmonella enterica serovar Infantis strain 1326/28Φ r stimulates neutrophil migration into the intestine, which rapidly protects the pigs against a subsequent (normally lethal) challenge with S. enterica serovar Typhimurium strain F98. Here we show that inoculation with either 1326/28Φ r or F98 activated reactive oxygen species (ROS) in neutrophils via NADPH pathways in vivo and in vitro and that the survival of both Salmonella strains was increased if neutrophils were cocultured with the ROS inhibitor N -acetylcysteine (captopril). Neither F98 nor 1326/28Φ r significantly increased reactive nitrogen species (RNS) levels in neutrophils isolated from uninfected pigs. Our results indicate the following: (i) rapid protection of highly susceptible gnotobiotic piglets against F98-induced gastroenteritis by preinoculation with 1326/28Φ r is likely to be due to stimulation of ROS-producing neutrophils in the intestinal epithelium prior to challenge with the lethal strain; (ii) pathological lesions of the intestine during severe gastroenteritis are not necessarily induced by neutrophil migration per se; and (iii) if neutrophil migration into the intestine is responsible for pathology, then neither increased production of ROS or RNS (in pigs inoculated with the lethal strain) nor reduced production (in protected pigs in which pathological lesions are ameliorated by preinoculation with 1326/28Φ r ) can account for this phenomenon.