AsianScientist (May 21, 2015) – A new Australian study shows that cells which form the bulk of our fast-acting ‘innate’ immune system behave differently, depending on whether an injury is infected or not.
Using a mouse model expressing photoconvertible proteins in neutrophils, Mr. Henry Hampton and Dr. Tatyana Chtanova, from the Garvan Institute of Medical Research, showed that neutrophils undertake their journey to lymph nodes within eight hours of infection. The findings have been published in the journal Nature Communications.
It is well known that paparazzi-like ‘neutrophils’ swarm to sites of injury within minutes to undertake damage control and kill invaders. Most have very short lives and self-destruct once their job is done.
Researchers now demonstrate that in certain cases neutrophils can also enlist reinforcements in their fight against pathogens. If the injury is infected, neutrophils seek out accomplices from the slower-acting ‘adaptive’ immune system by travelling to the nearest lymph node, sometimes carrying a sample of bacteria, or other microbe. This helps prime other types of immune cell for attack.
“There have been indirect studies and speculation, hinting at a downstream role for neutrophils. Thanks to our photoconvertible system, we’re the first ones to label neutrophils and see what they actually do, apart from immediate damage control,” said Chtanova, the project leader.
To investigate different neutrophil responses, Hampton and Chtanova induced either sterile or bacterial inflammation on the ears of mice. Bright light shone on the site of inflammation changed the color of ‘recruited’ neutrophils from green to red.
Cell-sorting technology picked up any color-converted red neutrophils that had moved from the site of infection to lymph nodes. Two-photon microscopy revealed that neutrophils traveled via the lymphatic system, rather than the bloodstream.
“Neutrophils together with T cells will try to clean up infection everywhere, including in the lymph node. Microbes from infection sites can migrate to the lymph node in the lymph stream, separately from neutrophils, so T cell recruitment by neutrophils may help prevent microbial spread,” said Chtanova.
“We can see that neutrophils bring microbes to the lymph node and that T cells proliferate as a result. While we have yet to identify the exact mechanisms that neutrophils use to communicate with T cells, we did uncover molecules involved in neutrophil migration from infected lesions to lymph nodes.”
Chtanova is optimistic about the implications of their research in gaining a better understanding of how the human immune system functions and reacts to infection.
“In theory, this new finding could help us prevent microbes from exploiting neutrophils as Trojan horses to spread infection. It might also allow us to enhance neutrophil migration and so generate a faster and more effective anti-microbial response.”
“At the very least, the finding helps clarify an aspect of how the innate and adaptive arms of the immune system work together in the initial stages of infection.”
The article can be found at: Hampton et al. (2015) Microbe-dependent Lymphatic Migration Of Neutrophils Modulates Lymphocyte Proliferation In Lymph Nodes.
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Source: The Garvan Institute of Medical Research.
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