Impaired Macrophage Function Underscores Susceptibility to Salmonella in Mice Lacking Irgm1 (LRG-47)

作者: Stanley C. Henry , Xiaojou Daniell , Maanasa Indaram , John F. Whitesides , Gregory D. Sempowski

DOI: 10.4049/JIMMUNOL.179.10.6963

关键词:

摘要: IRG proteins, or immunity-related GTPases (also known as p47 GTPases), are a group of IFN-regulated proteins that highly expressed in response to infection. The localize intracellular membranes including vacuoles contain pathogens infected macrophages and other host cells. Current data indicate the protein Irgm1 (LRG-47) is critical for resistance bacteria. This function thought be consequence regulating survival vacuolar bacteria In current work, role controlling Salmonella typhimurium was explored further define mechanism through which regulates resistance. Irgm1-deficient mice displayed increased susceptibility this bacterium reflected bacterial loads spleen liver decreased maturation S. granulomas. also an inability concentrate at sites deposition. vitro, ability suppress growth impaired. Furthermore, adhesion motility after activation with IFN-γ markedly decreased. Altered adhesion/motility those cells accompanied by changes cell morphology, density adhesion-associated actin staining. Together, these suggest addition pathogen-containing vacuoles, plays key activated macrophages.

参考文章(42)
C. Wray, W.J. Sojka, Experimental Salmonella typhimurium infection in calves. Research in Veterinary Science. ,vol. 25, pp. 139- 143 ,(1978) , 10.1016/S0034-5288(18)32968-0
M Gilly, R Wall, The IRG-47 gene is IFN-gamma induced in B cells and encodes a protein with GTP-binding motifs. Journal of Immunology. ,vol. 148, pp. 3275- 3281 ,(1992)
D. A. Carlow, Hung-Sia Teh, J. Marth, I. Clark-Lewis, Isolation of a gene encoding a developmentally regulated T cell-specific protein with a guanine nucleotide triphosphate-binding motif. Journal of Immunology. ,vol. 154, pp. 1724- 1734 ,(1995)
Carl G. Feng, Carmen M. Collazo-Custodio, Michael Eckhaus, Sara Hieny, Yasmine Belkaid, Karen Elkins, Dragana Jankovic, Gregory A. Taylor, Alan Sher, Mice Deficient in LRG-47 Display Increased Susceptibility to Mycobacterial Infection Associated with the Induction of Lymphopenia Journal of Immunology. ,vol. 172, pp. 1163- 1168 ,(2004) , 10.4049/JIMMUNOL.172.2.1163
Lisbeth Guethlein, Agnes Fütterer, Klaus Pfeffer, Annette Schaub, Kural Ozbek, Ulrich Boehm, Thorsten Klamp, Jonathan C. Howard, Two families of GTPases dominate the complex cellular response to IFN-gamma. Journal of Immunology. ,vol. 161, pp. 6715- 6723 ,(1998)
Alun C. Kirby, Ulf Yrlid, Mary Jo Wick, The Innate Immune Response Differs in Primary and Secondary Salmonella Infection Journal of Immunology. ,vol. 169, pp. 4450- 4459 ,(2002) , 10.4049/JIMMUNOL.169.8.4450
William P. Lafuse, David Brown, Lynn Castle, Bruce S. Zwilling, Cloning and characterization of a novel cDNA that is IFN-gamma-induced in mouse peritoneal macrophages and encodes a putative GTP-binding protein. Journal of Leukocyte Biology. ,vol. 57, pp. 477- 483 ,(1995) , 10.1002/JLB.57.3.477
Revathy C. Uthaiah, Gerrit J. K. Praefcke, Jonathan C. Howard, Christian Herrmann, IIGP1, an interferon-γ inducible 47-kDa GTPase of the mouse, showing cooperative enzymatic activity and GTP-dependent multimerization Journal of Biological Chemistry. ,vol. 278, pp. 29336- 29343 ,(2003) , 10.1074/JBC.M211973200
G. Govoni, P. Gros, Macrophage NRAMP1 and its role in resistance to microbial infections Inflammation Research. ,vol. 47, pp. 277- 284 ,(1998) , 10.1007/S000110050330
Sascha Martens, Iana Parvanova, Jens Zerrahn, Gareth Griffiths, Gudrun Schell, Gaby Reichmann, Jonathan C Howard, Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases. PLOS Pathogens. ,vol. 1, pp. 187- 201 ,(2005) , 10.1371/JOURNAL.PPAT.0010024