Selective Infection of Antigen-Specific B Lymphocytes by Salmonella Mediates Bacterial Survival and Systemic Spreading of Infection |
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Authors: | Yuri Souwer Alexander Griekspoor Jelle de Wit Chiara Martinoli Elena Zagato Hans Janssen Tineke Jorritsma Yotam E. Bar-Ephra?m Maria Rescigno Jacques Neefjes S. Marieke van Ham |
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Affiliation: | 1. Department of Immunopathology, Sanquin Blood Supply, Division Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; 2. Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; 3. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.; National Jewish Health and University of Colorado School of Medicine, United States of America, |
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Abstract: | BackgroundThe 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.Methodology/Principal FindingsHuman 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/SignificanceThis 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. |
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