Pathogenesis of Salmonella typhimurium and interactions with porcine neutrophils

Carrier swine infected with Salmonella typhimurium provide a reservoir of infection for humans and domestic animals. Reduction of the carrier state is desirable, but little is known about the bacterial-host interactions that influence the carrier state in swine. Interactions of S. typhimurium and porcine neutrophils were examined, and the effect of a [delta]cya[delta]crp mutant of S. typhimurium on subsequent wild-type colonization of swine was evaluated;When compared to those from unexposed controls, neutrophils from pigs orally exposed to S. typhimurium demonstrated reduced oxidative metabolism, measured by cytochrome C reduction and iodination; reduced motility, measured by random migration and chemotaxis; and reduced antibody-dependent cell-mediated cytotoxicity (ADCC) 1-2 days after exposure. Function normalized after 3-4 days, but iodination and ADCC were depressed again 7-14 days after exposure. Neutrophil bactericidal activity against S. typhimurium was enhanced in Salmonella-infected pigs 1-14 days after exposure;Treatment of pigs with bacillus Calmette-Guerin (BCG) before exposure to S. typhimurium did not reverse Salmonella-induced alterations in neutrophil function nor did it alter the colonization pattern and persistence of S. typhimurium in porcine internal organs;Bactericidal efficiency of porcine neutrophils against S. typhimurium was affected by bacterial opsonization, incubation interval, bacterial mutations, and by pre-treatment of neutrophils with recombinant human tumor necrosis factor alpha (TNF[alpha]). Opsonization enhanced bactericidal efficiency 0.5-2 hours after exposure, but this enhancement was decreased or lost by 3-4 hours. A phoP mutation in S. typhimurium conferred increased sensitivity to bactericidal activity. TNF[alpha] treatment caused a decrease in bactericidal efficiency 0.5-1 hour after exposure to S. typhimurium. This inhibition diminished by 2-3 hours, and bactericidal efficiency of TNF[alpha]-treated neutrophils was enhanced over nontreated neutrophils by 4 hours;Oral exposure of swine to a [delta]cya[delta]crp mutant of S. typhimurium ([chi]4233) caused a mild fever and soft feces. However, pigs previously exposed to [chi]4233 exhibited a milder clinical response to subsequent wild-type challenge than did pigs not exposed to [chi]4233. Ileal populations of wild-type S. typhimurium in [chi]4233-exposed pigs were 100- to 10,000-fold less than those in pigs not receiving [chi]4233. The liver, spleen, and ileocolic lymph nodes were cleared of wild-type S. typhimurium more quickly in [chi]4233-exposed pigs