title: Selective infection of antigen-specific B lymphocytes by Salmonella mediates bacterial survival and systemic spreading of infection.
abstract: BACKGROUND
  The bacterial pathogen Salmonella causes worldwide disease. A major route of intestinal entry involves M cells, providing access to B cell-rich Peyer's Patches. Primary human B cells phagocytose Salmonella typhimurium upon recognition by the specific surface Ig receptor (BCR). As it is unclear how Salmonella disseminates systemically, we studied whether Salmonella can use B cells as a transport device for spreading.
  
  
  RESULTS
  Human primary B cells or Ramos cell line were incubated with GFP-expressing Salmonella. Intracellular survival and escape was studied in vitro by live cell imaging, flow cytometry and flow imaging. HEL-specific B cells were transferred into C57BL/6 mice and HEL-expressing Salmonella spreading in vivo was analyzed investigating mesenteric lymph nodes, spleen and blood. After phagocytosis by B cells, Salmonella survives intracellularly in a non-replicative state which is actively maintained by the B cell. Salmonella is later excreted followed by reproductive infection of other cell types. Salmonella-specific B cells thus act both as a survival niche and a reservoir for reinfection. Adoptive transfer of antigen-specific B cells before oral infection of mice showed that these B cells mediate in vivo systemic spreading of Salmonella to spleen and blood.
  
  
  CONCLUSIONS
  This is a first example of a pathogenic bacterium that abuses the antigen-specific cells of the adaptive immune system for systemic spreading for dissemination of infection.
authors.affiliation: Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Souwer
authors.forename: Alexander
authors.initials: A
authors.lastname: Griekspoor
authors.forename: Jelle
authors.initials: J
authors.lastname: de Wit
authors.forename: Chiara
authors.initials: C
authors.lastname: Martinoli
authors.forename: Elena
authors.initials: E
authors.lastname: Zagato
authors.forename: Hans
authors.initials: H
authors.lastname: Janssen
authors.forename: Tineke
authors.initials: T
authors.lastname: Jorritsma
authors.forename: Yotam E
authors.initials: YE
authors.lastname: Bar-Ephraïm
authors.forename: Maria
authors.initials: M
authors.lastname: Rescigno
authors.forename: Jacques
authors.initials: J
authors.lastname: Neefjes
authors.forename: S Marieke
authors.initials: SM
authors.lastname: van Ham
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000502:physiology; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity*