title: Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+/+ mice and can be reactivated by IFNgamma neutralization.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA. dmonack@leland.stanford.edu
authors.forename: Denise M
authors.initials: DM
authors.lastname: Monack
authors.forename: Donna M
authors.initials: DM
authors.lastname: Bouley
authors.forename: Stanley
authors.initials: S
authors.lastname: Falkow
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D002908:Chronic Disease; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009500:Neutralization Tests; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D013997:Time Factors; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D007371:Interferon-gamma; D000099173:Natural Resistance-associated Macrophage Protein 1