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Immune cells outsmart bacterial infection by dying, Penn Vet study shows
Date:5/5/2014

A new study led by scientists at the University of Pennsylvania School of Veterinary Medicine has painted a clearer picture of the delicate arms race between the human immune system and a pathogen that seeks to infect and kill human cells.

The research explores the strategies by which the bacterial pathogen Yersinia, responsible for causing plague and gastrointestinal infections, tries to outsmart immune cell responses and looks at the tactics used by the immune system to fight back.

The senior author of the paper, which appears online this week in Proceedings of the National Academy of Sciences, is Igor E. Brodsky, an assistant professor in the Department of Pathobiology at Penn Vet. He teamed with Penn Vet's Naomi H. Philip, Annelise Snyder, Meghan Wynosky-Dolfi, Erin E. Zwack, Baofeng Hu, Louise FitzGerald and Elizabeth A. Mauldin. Alan M. Copenhaver and Sunny Shin of Penn's Perelman School of Medicine were also co-authors.

The researchers set out to try to solve a seeming paradox. They knew that one way Yersinia bacteria attempted to evade immune response was by using a protein called YopJ to block a key immune signaling pathway in host immune cells, the NF-κB pathway. Activation of this pathway by microbial infection causes infected cells to release signaling molecules, called cytokines, which mobilize the immune system to fight off infection. Yet, despite this strategic blockade, Yersinia infections do lead to recruitment of immune cells and inflammation, and the infected cells die.

In addition, previous experiments showed that a mutant version of Yersinia containing a particularly potent form of YopJ was better than the normal bacteria at killing cells in culture but paradoxically worse at causing disease in animal infections.

"So that led us to the hypothesis that maybe cell death was actually a host cell response," Brodsky said.

In other words, the researchers wondered whether the imm
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Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert

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