Type

Journal Article

Authors

Matthias Eberl
Bernhard Moser
Nicholas Topley
David W. Johnson
Simon J. Davies
John D. Williams
Tanya Parish
Colin Hill
Cormac G. Gahan
Mark A. Toleman
and 6 others

Subjects

Microbiology

Topics
t cell fosmidomycin tumor necrosis factor phagocytosed bacteria peritonitis hmb pp chemokines neutrophil

Human neutrophil clearance of bacterial pathogens triggers anti-microbial γδ T cell responses in early infection (2011)

Abstract Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria toproduce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact ofVc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.
Collections Ireland -> University College Cork -> Research Institutes and Centres
Ireland -> University College Cork -> Microbiology
Ireland -> University College Cork -> College of Science, Engineering and Food Science
Ireland -> University College Cork -> Alimentary Pharmabiotic Centre
Ireland -> University College Cork -> Microbiology - Journal Articles
Ireland -> University College Cork -> Alimentary Pharmabiotic Centre - Journal Articles

Full list of authors on original publication

Matthias Eberl, Bernhard Moser, Nicholas Topley, David W. Johnson, Simon J. Davies, John D. Williams, Tanya Parish, Colin Hill, Cormac G. Gahan, Mark A. Toleman and 6 others

Experts in our system

1
Matthias Eberl
University College Cork
Total Publications: 4
 
2
Colin Hill
University College Cork
Total Publications: 351
 
3
Cormac G M Gahan
University College Cork
Total Publications: 109