OCT 01, 2017 6:13 PM PDT

Cells Can Die When Infected so Others Can Live

WRITTEN BY: Carmen Leitch

Pathogens have a variety of tactics to avoid detection by our immune system, which is always surveilling our bodies for foreign invaders. New research has revealed a backup plan that cells use when the immune response is being evaded. Scientists have long wondered how a host organism is still able to fight infection when the pathogen is using a tactic meant to turn off host immunity. This work, led by Igor E. Brodsky of the University of Pennsylvania, and reported in the Journal of Experimental Medicine, addresses that question; it suggests that cell death helps limit invaders.

Mice infected with the bacteria Yersinia pseudotuberculosis form granulomas -- structures that confine pathogens. But those with a mutant form of the RIPK1 enzyme, rendering cells unable to undergo a particular form of cell death called apoptosis, do not. Researchers believe this RIPK1-induced apoptosis is a strategy that helps dying cells alert their neighbors that an infection is present. / Credit: University of Pennsylvania

"In the context of an infection, the cells that are dying are talking to the other cells that aren't infected," said the senior author of the work, Brodsky, an Assistant Professor in the Department of Pathobiology in Penn's School of Veterinary Medicine. "I don't think of it as altruistic, exactly, but it's a way for the cells that can't respond any longer to still alert their neighbors that a pathogen is present."

Some species of Yersinia bacteria can cause gastrointestinal disease and plague in humans and can inject a protein into infected host cells that allow the bacteria to avoid being detected by the immune system. That protein, YopJ, interferes with important cellular signaling cascades, halting the production of cytokines, which would usually notify other cells about the infection and induce apoptosis. Apoptosis is a type of cell death that was thought to be non-inflammatory. However, mice and humans can survive infections from Yersinia, because the immune response is still activated somehow. 

The researchers wanted to investigate how cells evade Yersinia's strategic protein and focused on an enzyme called RIPK1. It is known to have an important role in inducing cell death and signaling after pathogen detection.

"RIPK1 sits at a key decision point for the cell," explained Brodsky. "Depending on the stimuli the cells see, this protein can transduce a signal to activate gene expression, programmed cell death, or apoptosis, or it can activate another form of cell death called programmed necrosis."

Recent work reported in Nature Cell Biology outlined how RIPK1 assists a cell in switching between promoting survival- or death-associated functions. Although it’s known that disruption in this pathway can induce cell death, it was not known why. The scientists turned to a GlaxoSmithKline mouse in which RIPK1 is mutated, finding that the mutated RIPK1 protein cannot induce apoptosis when it encounters Yersinia bacteria.

"This mouse was really useful for us to be able to distinguish between the inflammatory response and apoptosis," Brodsky noted.

Apoptosis is usually seen as non-inflammatory, but the research showed that RIPK1-induced apoptosis can promote the production of cytokines on its own, possibly by nearby uninfected cells. This helps to initiate an inflammatory response and helps promote survival of the host.

The researchers want to continue to learn more about how cells initiate the production of cytokines by local cells, as well as how this work may be used to induce cancer cells to die.

Learn more about apoptosis from the video.

Sources: AAAS/Eurekalert! Via University of Pennsylvania, Journal of Experimental Medicine

About the Author
BS
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JUL 08, 2022
Immunology
Solving the Mystery of Failed Staph Vaccines Shows How to Make Them Effective
JUL 08, 2022
Solving the Mystery of Failed Staph Vaccines Shows How to Make Them Effective
Some common bacteria like Staphylococcus aureus have both harmless and pathogenic versions. While staph is often harmles ...
JUL 25, 2022
Cancer
Does the Secret to Immunotherapy Lie in...Poop?
JUL 25, 2022
Does the Secret to Immunotherapy Lie in...Poop?
Advancements in immunotherapy have proven instrumental in reshaping the face of cancer research in recent years.  W ...
AUG 02, 2022
Neuroscience
Could Common Viruses be Triggering Alzheimer's?
AUG 02, 2022
Could Common Viruses be Triggering Alzheimer's?
Recent allegations of research misconduct have called years of Alzheimer's research into question. The controversy surro ...
AUG 05, 2022
Immunology
A High-Protein Diet Seems to Change the Microbiome & Activate Immunity
AUG 05, 2022
A High-Protein Diet Seems to Change the Microbiome & Activate Immunity
The microbiome has a powerful influence on human well-being and disease. It might also be a useful way to approach disea ...
AUG 06, 2022
Coronavirus
Mandated Masking & Vaccination Gets a University Back to 'Normal'
AUG 06, 2022
Mandated Masking & Vaccination Gets a University Back to 'Normal'
Students at Boston University were told to get vaccinated and wear masks on campus. That has allowed people to attend cl ...
SEP 20, 2022
Microbiology
Manuka Honey Helps Treat Drug Resistant Lung Infections
SEP 20, 2022
Manuka Honey Helps Treat Drug Resistant Lung Infections
Drug resistant bacterial infections are expected to increase, and these dangerous illnesses already claim the lives of t ...
Loading Comments...