Genetic determinants of acute inflammation regulate Salmonella infection and modulate Slc11a1 gene (formerly Nramp1) effects in selected mouse lines.
Two lines of mice selected to produce maximal (AIRmax) or minimal (AIRmin) acute inflammatory reactions (AIR) differ in their susceptibility to infection by Salmonella enterica serotype Typhimurium (S. Typhimurium). The LD(50) for AIRmax mice is 1000 times higher than that observed for AIRmin mice, and higher frequencies of Slc11a1 alleles (known to confer either resistance (R) or high susceptibility (S) to S. Typhimurium) were consistently found in AIRmax and AIRmin mouse lines, respectively. In order to evaluate the effect of the quantitative trait loci (QTL) segregated in AIRmax and AIRmin mice on Slc11a1 dependent susceptibility to S. Typhimurium, the R and S alleles were fixed in homozygosity in AIRmax and AIRmin backgrounds by genotype assisted breedings. These new lines were named AIRmax(RR), AIRmax(SS), AIRmin(RR), and AIRmin(SS). Acute inflammation of Slc11a1(RR) animals was more severe in comparison to their Slc11a1(SS) counterparts, implicating Slc11a1 (or other linked genes) in AIR regulation. The LD(50) of S. Typhimurium was 800-times higher for AIRmax(SS) than for AIRmin(SS), demonstrating that AIR QTL can act as modifiers of the Slc11a1(SS) susceptibility gene. Four microsatellite markers for S. Typhimurium susceptibility QTL described in other mouse lines showed specific allele fixation in AIRmax or AIRmin mice, suggesting that these chromosomal regions also segregate with inflammatory phenotypes.
Borrego
Andrea
A
Laboratório de Imunogenética - Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, SP 05503900, Brazil.
Peters
Luciana Carla
LC
Jensen
José Ricardo
JR
Ribeiro
Orlando Garcia
OG
Koury Cabrera
Wafa Hanna
WH
Starobinas
Nancy
N
Seman
Michel
M
Ibañez
Olga Martinez
OM
De Franco
Marcelo
M
D000210:Acute-Phase Reaction; D000483:Alleles; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics* / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007113:Immunity, Innate; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci; D012481:Salmonella Infections, Animal / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012486:Salmonella typhimurium; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1