Genetic determinants of acute inflammation regulate Salmonella infection and modulate Slc11a1 gene (formerly Nramp1) effects in selected mouse lines |
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| Authors: | Borrego Andrea Peters Luciana Carla Jensen José Ricardo Ribeiro Orlando Garcia Koury Cabrera Wafa Hanna Starobinas Nancy Seman Michel Ibañez Olga Martinez De Franco Marcelo |
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| Affiliation: | 1. Laboratório de Imunogenética – Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, SP 05503900, Brazil;2. Serviço de Parasitologia, Instituto Adolfo Lutz, São Paulo, SP, Brazil;3. INSERM U519-Faculté de Médicine et de Pharmacie, Université de Rouen, Rouen, France;1. University of Idaho, Department of Biological Sciences & Center for Reproductive Biology, United States;2. Columbia River Inter-Tribal Fish Commission, Portland, Oregon, United States;1. Molecular Biosciences, University of Texas at Austin, Austin, TX 78713, USA;2. Waggoner Center for Alcohol & Addiction Research, University of Texas at Austin, Austin, TX 78713, USA;3. Ophthalmology and Visual Science, University of Texas Health Science Center at Houston, Houston, TX 77030, USA;1. IFP Energies Nouvelles, 1 et 4 Avenue de Bois-Préau, 92852 Rueil-Malmaison Cedex, France;2. Aix-Marseille Univ, CNRS, Centrale Marseille, M2P2, Marseille, France;3. TU Dortmund University, Laboratory of Fluid Separations, 44221 Dortmund, Germany;4. Norwegian University of Science and Technology, Department of Chemistry, NO 7491 Trondheim, Norway;5. Ecole Polytechnique Fédérale de Lausanne, Valais-Wallis, CH-1951 Sion, Switzerland;6. ProSim SA, Immeuble Stratege A, 51 rue Ampere, F-31670 Labege, France;7. Department of Chemical and Biochemical Engineering, Technical University of Denmark, DK-2800 Lyngby, Denmark;1. Department of Paediatrics, SRM Medical College Hospital and Research Centre, Kattankulathur, India;2. Dept of Genetics, Dr. ALM PG IBMS, University of Madras, Taramani, Chennai 600113, India;1. COPPE - Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;2. INRIA and LIRMM, Montpellier, France |
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| Abstract: | 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. |
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