Dissemination of persistent intestinal bacteria via the mesenteric lymph nodes causes typhoid relapse.
Enteric pathogens can cause relapsing infections in a proportion of treated patients, but greater understanding of this phenomenon is hindered by the lack of appropriate animal models. We report here a robust animal model of relapsing primary typhoid that initiates after apparently successful antibiotic treatment of susceptible mice. Four days of enrofloxacin treatment were sufficient to reduce bacterial loads below detectable levels in all major organs, and mice appeared otherwise healthy. However, any interruption of further antibiotic therapy allowed renewed fecal shedding and renewed bacterial growth in systemic tissues to occur, and mice eventually succumbed to relapsing infection. In vivo imaging of luminescent Salmonella identified the mesenteric lymph nodes (MLNs) as a major reservoir of relapsing infection. A magnetic-bead enrichment strategy isolated MLN-resident CD11b(+) Gr-1(-) monocytes associated with low numbers of persistent Salmonella. However, the removal of MLNs increased the severity of typhoid relapse, demonstrating that this organ serves as a protective filter to restrain the dissemination of bacteria during antibiotic therapy. Together, these data describe a robust animal model of typhoid relapse and identify an important intestinal phagocyte subset involved in protection against the systemic spread of enteric infection.
Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, McGuire Translational Research Facility, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Amanda J
AJ
Griffin
Lin-Xi
LX
Li
Sabrina
S
Voedisch
Oliver
O
Pabst
Stephen J
SJ
McSorley
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002469:Cell Separation; D004195:Disease Models, Animal; D000077422:Enrofloxacin; D005434:Flow Cytometry; D024841:Fluoroquinolones / Q000627:therapeutic use; D007421:Intestine, Small / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology*; D008643:Mesentery / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000382:microbiology*; D012008:Recurrence; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D012485:Salmonella typhi / Q000276:immunology
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077422:Enrofloxacin
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