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Impaired macrophage function underscores susceptibility to Salmonella in mice lacking Irgm1 (LRG-47).

Publication ,  Journal Article
Henry, SC; Daniell, X; Indaram, M; Whitesides, JF; Sempowski, GD; Howell, D; Oliver, T; Taylor, GA
Published in: J Immunol
November 15, 2007

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

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

November 15, 2007

Volume

179

Issue

10

Start / End Page

6963 / 6972

Location

United States

Related Subject Headings

  • Vacuoles
  • Spleen
  • Salmonella typhimurium
  • Salmonella Infections, Animal
  • Mice, Knockout
  • Mice
  • Macrophages
  • Macrophage Activation
  • Liver
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Henry, S. C., Daniell, X., Indaram, M., Whitesides, J. F., Sempowski, G. D., Howell, D., … Taylor, G. A. (2007). Impaired macrophage function underscores susceptibility to Salmonella in mice lacking Irgm1 (LRG-47). J Immunol, 179(10), 6963–6972. https://doi.org/10.4049/jimmunol.179.10.6963
Henry, Stanley C., Xiaojou Daniell, Maanasa Indaram, John F. Whitesides, Gregory D. Sempowski, David Howell, Tim Oliver, and Gregory A. Taylor. “Impaired macrophage function underscores susceptibility to Salmonella in mice lacking Irgm1 (LRG-47).J Immunol 179, no. 10 (November 15, 2007): 6963–72. https://doi.org/10.4049/jimmunol.179.10.6963.
Henry SC, Daniell X, Indaram M, Whitesides JF, Sempowski GD, Howell D, et al. Impaired macrophage function underscores susceptibility to Salmonella in mice lacking Irgm1 (LRG-47). J Immunol. 2007 Nov 15;179(10):6963–72.
Henry, Stanley C., et al. “Impaired macrophage function underscores susceptibility to Salmonella in mice lacking Irgm1 (LRG-47).J Immunol, vol. 179, no. 10, Nov. 2007, pp. 6963–72. Pubmed, doi:10.4049/jimmunol.179.10.6963.
Henry SC, Daniell X, Indaram M, Whitesides JF, Sempowski GD, Howell D, Oliver T, Taylor GA. Impaired macrophage function underscores susceptibility to Salmonella in mice lacking Irgm1 (LRG-47). J Immunol. 2007 Nov 15;179(10):6963–6972.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

November 15, 2007

Volume

179

Issue

10

Start / End Page

6963 / 6972

Location

United States

Related Subject Headings

  • Vacuoles
  • Spleen
  • Salmonella typhimurium
  • Salmonella Infections, Animal
  • Mice, Knockout
  • Mice
  • Macrophages
  • Macrophage Activation
  • Liver
  • Immunology