The Journal of Experimental Medicine
Symposium on Dendritic Cells
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Published 20 January 2004. doi:10.1084/jem.20031319
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 2, 231-241
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Salmonella typhimurium Persists within Macrophages in the Mesenteric Lymph Nodes of Chronically Infected Nramp1+/+ Mice and Can Be Reactivated by IFN{gamma} Neutralization

Denise M. Monack1, Donna M. Bouley2, and Stanley Falkow1

1 Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305
2 Department of Comparative Medicine, Stanford School of Medicine, Stanford University, Stanford, CA 94305

Address correspondence to D.M. Monack, Dept. of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305. Phone: (650) 723-2671; Fax: (650) 723-1837; email: dmonack{at}leland.stanford.edu

Host-adapted strains of Salmonella are capable of establishing a persistent infection in their host often in the absence of clinical disease. The mouse model of Salmonella infection has primarily been used as a model for the acute systemic disease. Therefore, the sites of long-term S. typhimurium persistence in the mouse are not known nor are the mechanisms of persistent infection clearly understood. Here, we show that S. typhimurium can persist for as long as 1 yr in the mesenteric lymph nodes (MLNs) of 129sv Nramp1+/+ (Slc11a1+/+) mice despite the presence of high levels of anti–S. typhimurium antibody. Tissues from 129sv mice colonized for 60 d contain numerous inflammatory foci and lesions with features resembling S. typhi granulomas. Tissues from mice infected for 365 d have very few organized inflammatory lesions, but the bacteria continue to persist within macrophages in the MLN and the animals generally remain disease-free. Finally, chronically infected mice treated with an interferon-{gamma} neutralizing antibody exhibited symptoms of acute systemic infection, with evidence of high levels of bacterial replication in most tissues and high levels of fecal shedding. Thus, interferon-{gamma}, which may affect the level of macrophage activation, plays an essential role in the control of the persistent S. typhimurium infection in mice.

Key Words: persistence • Slc11a1 • carriage • interferon-{gamma} • monocytes


Abbreviations used in this paper: IVIS, in vivo imaging system; MLN, mesenteric LN; RES, reticuloendothelial system.


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