Salmonella Typhimurium

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  Project Leader
  Professor Dick Strugnell

  rastru@unimelb.edu.au

  View researcher's webpage

  +61 3 8344 8479

Project Details

Salmonella Typhimurium is an intracellular bacterium that replicates with macrophages, specialised cells designed to 'clean' the blood of pathogenic organisms. The intracellular location means that many antibiotics are ineffective, and vaccines dependent on T lymphocytes, which are important to host immunity to reinfection. We are currently examining how the bacterium can persist inside cells like macrophages and the metabolic processes the bacterium uses to facilitate intracellular replication. Our experience in manipulating Salmonella and its use in vaccination against Salmonella disease, and as a 'vector' for vaccination against unrelated pathogens, has been exploited in the search for new human vaccines.

Recent research highlights:

1. Contribution of Thy1+ NK cells to protective IFN-γ production during Salmonella Typhimurium infections.
   Kupz A, Scott TA, Belz GT, Andrews DM, Greyer M, Lew AM, Brooks AG, Smyth MJ, Curtiss R, Bedoui S, Strugnell RA.
   Proc Natl Acad Sci USA 2013; 110(6): 2252-7.
   IFN-γ is critical for immunity against infection with Salmonella Typhimurium, although its cellular source remains incompletely understood. We found that a critical source of protective IFN-γ during early Salmonella infection is Thy1-expressing natural killer (NK) cells, the antibacterial effector function of which is the strongest when the cells are immature but decreases as cells become terminally differentiated. In corroboration with recent reports, we noted that Thy1+ NK cells also contribute to immune memory during a secondary response to Salmonella.
2. NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8⁺ T cells
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   Kupz A, Guarda G, Gebhardt T, Sander LE, Short KR, Diavatopoulos DA, Wijburg OL, Cao H, Waithman JC, Chen W, Fernandez-Ruiz D, Whitney PG, Heath WR, Curtiss R 3rd, Tschopp J, Strugnell RA, Bedoui S.
   Nature Immunology 2012; 13(2): 162-9.
   Noncognate CD8+ memory T cells can be rapidly activated by Salmonella Typhimurium. Activated CD8+ memory T cells contribute to host immunity by secreting IFN-γ, which is dependent on flagellin-induced NLRC4 inflammasome activation in splenic dendritic cells. Two key cytokines, interleukin 18 (IL-18) and IL-1β, played important but distinct roles in NLRC-4 inflammasome activation. These findings provide a comprehensive mechanistic framework for the regulation of noncognate memory T cell responses during bacterial immunity.