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SUMMARY:Innate crosstalk of unconventional T cells\, monocytes and neutrop
 hils in bacterial infection - Dr Matthias Eberl\, University of Cardiff
DTSTART:20130501T113000Z
DTEND:20130501T123000Z
UID:TALK44582@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:Unconventional T-cells such as human blood γδ T-cells and MA
 IT cells\, monocytes and neutrophils share a responsiveness toward inflamm
 atory stimuli and rapidly accumulate at sites of infection.  Studying thei
 r interaction in vitro and relating these findings to in vivo observations
  in patients therefore provides crucial insight into inflammatory events. 
  \n\nOur data demonstrate that human γδ T-cells and MAIT cells readily r
 espond to neutrophils harboring phagocytosed bacteria\, as evidenced by ex
 pression of activation markers and secretion of pro-inflammatory cytokines
 .  This response appears to be dependent on the ability of these bacteria 
 to produce metabolites of the microbial non-mevalonate isoprenoid pathway 
 and the vitamin B2 pathway\, and requires cell-cell contact with accessory
  monocytes.  In turn\, both types of unconventional T-cells provide potent
  survival signals resulting in monocyte and neutrophil activation and diff
 erentiation.  We believe that the stimulation of unconventional T-cells at
  the site of infection amplifies the inflammatory response and has importa
 nt consequences for pathogen clearance and the development of microbe-spec
 ific immunity.  \n\nHowever\, if triggered at the wrong time or the wrong 
 place\, this rapid reaction toward bacteria may also lead to inflammation-
 related damage.  For instance\, patients with acute peritoneal-dialysis (P
 D)-associated bacterial peritonitis – characterized by an excessive infl
 ux of neutrophils and monocytes into the peritoneal cavity – show a sele
 ctive activation of local γδ T-cells depending on the presence of the no
 n-mevalonate pathway in the causative bacterial pathogens.  We find a simi
 lar activation of circulating γδ T-cells in patients with acute sepsis. 
  In both diseases\, the γδ T cell-driven perpetuation of inflammatory re
 sponses is associated with detrimental clinical outcomes.  \n\nOur finding
 s indicate a direct link between invading pathogens\, neutrophils\, monocy
 tes and microbe-responsive unconventional T-cells in early infection\, and
  suggest novel diagnostic and therapeutic approaches.\n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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