Pathogenesis of Salmonella typhimurium and interactions with porcine neutrophils

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Coe, Nancy
Major Professor
James A. Roth
Committee Member
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Veterinary Microbiology and Preventive Medicine
Our faculty promote the understanding of causes of infectious disease in animals and the mechanisms by which diseases develop at the organismal, cellular and molecular levels. Veterinary microbiology also includes research on the interaction of pathogenic and symbiotic microbes with their hosts and the host response to infection.
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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.

Wed Jan 01 00:00:00 UTC 1992