Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

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 to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/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.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

The Practice of Sheep Veterinary Medicine

This book is intended to be a reference text for veterinarians who provide clinical services to sheep producers. It is directed first and foremost at Australian sheep-raising systems, but the approaches described herein will have wide application in all countries where sheep are raised under extensive grazing conditions. Most of the important conditions of sheep in Australia are relatively straightforward to diagnose, but the establishment of effective and economically sound control strategies is often the most difficult part of health management, particularly for those who are less familiar with sheep production systems. With six initial chapters focusing on providing readers with a basic understanding of the business and science underpinning sheep production, this book focuses its remaining chapters on reproduction and disease conditions, ordered largely on a systems basis. The book provides details about the way disease processes develop and manifest in sheep flocks, with numerous references for those who wish to read further. Australian sheep production is a profitable and fulfilling agricultural pursuit for a large number of farm owners, and this book is intended to assist those who work in the industry to add to the profitability and efficiency of sheep production systems, the quality of sheep products and the welfare of the sheep in those systems

Research in Progress

Updates on research conducted by the Boston University School of Medicin

Redbook: 2005-2006

Advice compiled by Boston University School of Medicine students for incoming first year students and third or fourth year students preparing for clinical rotations

Redbook: 2004-2005

Advice compiled by Boston University School of Medicine students for incoming first year students and third or fourth year students preparing for clinical rotations

Third year survival guide: 1997-1998

Advice compiled by Boston University School of Medicine students for incoming first year students and third or fourth year students preparing for clinical rotations

Research in Progress

Updates on research conducted by the Boston University School of Medicin

Research in Progress

Updates on research conducted by the Boston University School of Medicin

Research in Progress

Updates on research conducted by the Boston University School of Medicin

Chiasma

Newspaper reporting on events at the Boston University School of Medicine in the 1960s