title: Listr1 locus regulates innate immunity against Listeria monocytogenes infection in the mouse liver possibly through Cxcl11 polymorphism.
abstract: Inbred stains of mice display differential susceptibility to infection with the common foodborne pathogen Listeria monocytogenes (Lm). Previously, Listr1 and Listr2, two genetic loci that control differential sensitivity to Lm infection between BALB/cByJ and C57BL/6ByJ mice, were identified. To analyze the role of Listr1 in innate immune responses, we employed congenic mice (C.B6By-Listr1/Rag2 (-/-) ) bearing the C57BL/6ByJ-derived Listr1 locus on a BALB/c-Rag2 (-/-) background. Consistent with the results of a previous genetic analysis, the congenic mice showed increased susceptibility to Lm infection. The bacterial burden in the liver between the congenic and control lines was significantly different (P < 0.05) from 24 h postinfection with Lm. Analysis of genes within the Listr1 locus identified a frameshift mutation in the Cxcl11 gene of the C57BL/6 strain that prevents production of the mature chemokine CXCL11. No differences in inflammatory cell infiltration or cells expressing CXCR3 and CXCR7 which are the receptors of CXCL11 occurred because of CXCL11 deficiency in the congenic mice spleens. However, these mice lacked a distinct population of CD14(+) positive resident mononuclear cells that express intermediate levels of CXCR3 and CXCR7 in the liver. There were fewer microabscesses in the liver of CXCL11-deficient mice during the early stage of infection, which is consistent with their decreased ability to resist Lm. Our results, when taken together, show that the Listr1 locus plays an important role in early control of Lm infection in the mouse liver and that Cxcl11 is a candidate gene for disease severity within this locus.
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, No. 92 Bei Er Ma Lu, Shenyang, Liaoning, 110001, China, zmqi@mail.cmu.edu.cn.
authors.forename: Zanmei
authors.initials: Z
authors.lastname: Qi
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Ji
authors.initials: J
authors.lastname: Yang
authors.forename: Guoming
authors.initials: G
authors.lastname: Zhao
authors.forename: Yaming
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D054371:Chemokine CXCL11 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity*; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011110:Polymorphism, Genetic; D054387:Receptors, CXCR / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D054371:Chemokine CXCL11; C501897:Cmkor1 protein, mouse; C515203:Cxcl11 protein, mouse; C515188:Cxcr3 protein, mouse; D018950:Lipopolysaccharide Receptors; D054387:Receptors, CXCR; D054367:Receptors, CXCR3