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

Abstract

Preinoculation of susceptible 5-day-old gnotobiotic piglets with Salmonella enterica serovar Infantis strain 1326/28⌽ 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 1326/28⌽ 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 1326/28⌽ 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 1326/28⌽ 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 1326/28⌽ r ) can account for this phenomenon.

Cytokine Response of Porcine Cell Lines to Salmonella enterica serovar Typhimurium and its hilA and ssrA mutants

“…However, this response, at least in gnotobiotic pigs, can be absent after infection with attenuated mutants (Splichal et al., 2005; Trebichavsky et al., 2006). From the vaccine design point of view it is desirable that the potential vaccine strain induces the inflammatory response as under some circumstances the inflammation and neutrophil infiltration may protect pigs from the superinfection with the wild‐type strain (Dlabac et al., 1997; Foster et al., 2003, 2005; Splichal et al., 2005).…”

Porcine Monocyte DNA Traps Formed during Infection with Pathogenic Clostridioides difficile Strains

“…In addition to preventing colonization by the avirulent strain, studies in pigs have shown that this approach can induce a rapid form of protection against clinical diarrhea [ 40 ] not related to colonization inhibition. This latter protective effect appears to involve an influx of neutrophils and macrophages into the site of colonization in the intestinal mucosa and involves production of antibacterial ROS at the site of the acute infection [ 41 ].…”

Commensal Bacteria Impact on Intestinal Toll-like Receptor Signaling in Salmonella-Challenged Gnotobiotic Piglets

“…One reason for the high effectivity of EcN could be its rough chemotype LPS (R-LPS) [80]. GN minipigs colonized with R-LPS S. Typhimurium F98 or S. Typhimurium SF1591 were resistant to subsequent infection with virulent S. Infantis 1326/28 [81,82] or S. Typhimurium LT2 [83], respectively. S. Typhimurium LT2 is avirulent for one-week-old CV piglets [53], which are protected by complex microbiota mediating their colonization resistance [26,27].…”