This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lang, T. Articles by Blackwell, J. M. Search for Related Content PubMed PubMed Citation Articles by Lang, T. Articles by Blackwell, J. M.

 Previous Article  |  Next Article 

Infect. Immun., Feb 1997, 380-386, Vol 65, No. 2
Copyright © 1997, American Society for Microbiology

Nramp1 transfection transfers Ity/Lsh/Bcg-related pleiotropic effects on macrophage activation: influence on antigen processing and presentation

T Lang, E Prina, D Sibthorpe and JM Blackwell
Unite d'Immunophysiologie Cellulaire, Institut Pasteur, Paris, France.

The natural resistance-associated macrophage protein (Nramp1) regulates macrophage activation. One of its pleiotropic effects on macrophage function is to regulate expression of major histocompatibility class II molecules. In this study macrophages stably transfected with the wild- type (infection-resistant) or the natural mutant (infection- susceptible) allele of the Nramp1 gene were used to study class II expression and processing and presentation of recombinant protein antigens to CD4+ T-cell hybridomas. As demonstrated previously for macrophages from Nramp1-resistant and -susceptible congenic mouse strains, transfected macrophage clones carrying the wild-type allele showed enhanced upregulation of class II molecules in response to gamma interferon compared to that shown by macrophage clones carrying an endogenous mutant allele or transfected with the mutant allele expressed under a viral long terminal repeat promoter. The wild-type allele-transfected macrophage clones also demonstrated an enhanced, lipopolysaccharide-dependent ability to process the recombinant leishmanial antigen LACK-delta 1 (the Leishmania homolog of receptors for activated C kinase) for presentation to LACK-specific CD4+ T cells. An influence on antigen processing must therefore be added to the growing list of pleiotropic effects of the Nramp1 gene potentially contributing to its role in infectious and autoimmune disease susceptibility. These results also have important implications for analysis of T-cell responses to vaccination, especially where antigens are presented to the immune system using live Salmonella species or Mycobacterium bovis BCG as a vaccine vehicle.

This article has been cited by other articles:

• Stober, C. B., Brode, S., White, J. K., Popoff, J.-F., Blackwell, J. M. (2007). Slc11a1, Formerly Nramp1, Is Expressed in Dendritic Cells and Influences Major Histocompatibility Complex Class II Expression and Antigen-Presenting Cell Function. Infect. Immun. 75: 5059-5067 [Abstract] [Full Text]  
• White, J. K., Mastroeni, P., Popoff, J.-F., Evans, C. A. W., Blackwell, J. M. (2005). Slc11a1-mediated resistance to Salmonella enterica serovar Typhimurium and Leishmania donovani infections does not require functional inducible nitric oxide synthase or phagocyte oxidase activity. J. Leukoc. Biol. 77: 311-320 [Abstract] [Full Text]  
• Clare, S., Goldin, R., Hale, C., Aspinall, R., Simmons, C., Mastroeni, P., Dougan, G. (2003). Intracellular Adhesion Molecule 1 Plays a Key Role in Acquired Immunity to Salmonellosis. Infect. Immun. 71: 5881-5891 [Abstract] [Full Text]  
• Kehres, D. G., Janakiraman, A., Slauch, J. M., Maguire, M. E. (2002). SitABCD Is the Alkaline Mn2+ Transporter of Salmonella enterica Serovar Typhimurium. J. Bacteriol. 184: 3159-3166 [Abstract] [Full Text]  
• Altet, L., Francino, O., Solano-Gallego, L., Renier, C., Sanchez, A. (2002). Mapping and Sequencing of the Canine NRAMP1 Gene and Identification of Mutations in Leishmaniasis-Susceptible Dogs. Infect. Immun. 70: 2763-2771 [Abstract] [Full Text]  
• Wardrop, S. L., Wells, C., Ravasi, T., Hume, D. A., Richardson, D. R. (2002). Induction of Nramp2 in activated mouse macrophages is dissociated from regulation of the Nramp1, classical inflammatory genes, and genes involved in iron metabolism. J. Leukoc. Biol. 71: 99-106 [Abstract] [Full Text]  
• Moisan, J., Wojciechowski, W., Guilbault, C., Lachance, C., Di Marco, S., Skamene, E., Matlashewski, G., Radzioch, D. (2001). Clearance of Infection with Mycobacterium bovis BCG in Mice Is Enhanced by Treatment with S28463 (R-848), and Its Efficiency Depends on Expression of Wild-Type Nramp1 (Resistance Allele). Antimicrob. Agents Chemother. 45: 3059-3064 [Abstract] [Full Text]  
• al-Ramadi, B. K., Al-Dhaheri, M. H., Mustafa, N., AbouHaidar, M., Xu, D., Liew, F. Y., Lukic, M. L., Fernandez-Cabezudo, M. J. (2001). Influence of Vector-Encoded Cytokines on Anti-Salmonella Immunity: Divergent Effects of Interleukin-2 and Tumor Necrosis Factor Alpha. Infect. Immun. 69: 3980-3988 [Abstract] [Full Text]  
• Gomes, N. A., Barreto-de-Souza, V., DosReis, G. A. (2000). Early in vitro priming of distinct Th cell subsets determines polarized growth of visceralizing Leishmania in macrophages. Int Immunol 12: 1227-1233 [Abstract] [Full Text]  
• Maliarik, M. J., Chen, K. M., Sheffer, R. G., Rybicki, B. A., Major, M. L., Popovich, J. Jr., Iannuzzi, M. C. (2000). The Natural Resistance-Associated Macrophage Protein Gene in African Americans with Sarcoidosis. Am. J. Respir. Cell Mol. Bio. 22: 672-675 [Abstract] [Full Text]  
• Fulton, S. A., Martin, T. D., Redline, R. W., Henry Boom, W. (2000). Pulmonary Immune Responses during Primary Mycobacterium bovis- Calmette-Guerin Bacillus Infection in C57Bl/6 Mice. Am. J. Respir. Cell Mol. Bio. 22: 333-343 [Abstract] [Full Text]  
• Wojciechowski, W., DeSanctis, J., Skamene, E., Radzioch, D. (1999). Attenuation of MHC Class II Expression in Macrophages Infected with Mycobacterium bovis Bacillus Calmette-Guerin Involves Class II Transactivator and Depends on the Nramp1 Gene. J. Immunol. 163: 2688-2696 [Abstract] [Full Text]  
• Chen, Z.-m., Jenkins, M. K. (1999). Clonal Expansion of Antigen-Specific CD4 T Cells following Infection with Salmonella typhimurium Is Similar in Susceptible (Itys) and Resistant (Ityr) BALB/c Mice. Infect. Immun. 67: 2025-2029 [Abstract] [Full Text]  
• Mastroeni, P., Clare, S., Khan, S., Harrison, J. A., Hormaeche, C. E., Okamura, H., Kurimoto, M., Dougan, G. (1999). Interleukin 18 Contributes to Host Resistance and Gamma Interferon Production in Mice Infected with Virulent Salmonella typhimurium. Infect. Immun. 67: 478-483 [Abstract] [Full Text]  
• Mastroeni, P., Harrison, J. A., Robinson, J. H., Clare, S., Khan, S., Maskell, D. J., Dougan, G., Hormaeche, C. E. (1998). Interleukin-12 Is Required for Control of the Growth of Attenuated Aromatic-Compound-Dependent Salmonellae in BALB/c Mice: Role of Gamma Interferon and Macrophage Activation. Infect. Immun. 66: 4767-4776 [Abstract] [Full Text]  
• Soo, S.-S., Villarreal-Ramos, B., Khan, C. M. A., Hormaeche, C. E., Blackwell, J. M. (1998). Genetic Control of Immune Response to Recombinant Antigens Carried by an Attenuated Salmonella typhimurium Vaccine Strain: Nramp1 Influences T-Helper Subset Responses and Protection against Leishmanial Challenge. Infect. Immun. 66: 1910-1917 [Abstract] [Full Text]