The mycotoxin deoxynivalenol promotes uptake of Salmonella Typhimurium in porcine macrophages, associated with ERK1/2 induced cytoskeleton reorganization.
Both the mycotoxin deoxynivalenol (DON) and Salmonella Typhimurium are major issues in swine production. This study aimed at examining the interaction between DON and Salmonella Typhimurium at the level of the porcine innate immune system, represented by macrophages. First, we assessed the direct cytotoxic effect of DON on porcine macrophages. Incubation with 0.25 microg/mL of DON or higher resulted in a significant cytotoxic effect after 24 h of incubation. Secondly, the direct toxic effect of DON on the growth and on the expression of Salmonella pathogenicity island 1 (SPI-1) and SPI-2 virulence genes of Salmonella Typhimurium was determined. At low non-cytotoxic concentrations, as can be found in the serum of pigs, DON did not have any effect on either growth or virulence gene expression of Salmonella Typhimurium. However, when the invasion and intracellular survival of Salmonella Typhimurium in macrophages preexposed to 0.025 microg/mL of DON was examined, DON significantly promoted the uptake of Salmonella Typhimurium into macrophages. The enhanced uptake coincided with marked F-actin reorganization of the cells, which was due to the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). These results suggest that low but relevant concentrations of DON modulate the innate immune system and could thus increase the susceptibility of pigs to infections with Salmonella Typhimurium.
Vandenbroucke
Virginie
V
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. virginie.vandenbroucke@agent.be
Croubels
Siska
S
Verbrugghe
Elin
E
Boyen
Filip
F
De Backer
Patrick
P
Ducatelle
Richard
R
Rychlik
Ivan
I
Haesebrouck
Freddy
F
Pasmans
Frank
F
D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D012486:Salmonella typhimurium / Q000502:physiology*; D013552:Swine; D014255:Trichothecenes / Q000494:pharmacology*
D000199:Actins; D014255:Trichothecenes; D048049:Extracellular Signal-Regulated MAP Kinases; C007262:deoxynivalenol