Zooming inside the immune system
An international team of researchers has filmed an immune cell becoming infected by a parasite. And it was able to chase it as the infection begins to spread throughout the body. Here is a quote from the lead scientist: 'Using multi-photon microscopy, we studied dendritic cells in the skin. Under normal conditions we found the cells in the epidermis (top layer) were static, whereas in the dermis (second layer) they were very active, moving around as though seeking out pathogens. Once we established this, it was fascinating to introduce the Leishmania infection and watch as the parasite was picked up by the cells and the process by which it began to spread throughout the body.' But read more...
The images on the left illustrate "the migratory mechanisms of DDC and LC and the response of DDC to systemic injection of PTX. The panels depict a representative cell under control and PTX treatment conditions, respectively. The red square indicates the cell centroid, and the red line shows movement of the centroid over the observation period (n = 3 experiments for PTX treatment)." (Credit: Weninger et al.) Here are some information about the acronyms used in the caption above: dendritic cells (DC), "including those of the skin, act as sentinels for intruding microorganisms." In the epidermis, they are named Langerhans cells (LC) while they're called dermal dendritic cells (DDC) in the dermis. And PTX is a pertussis toxin.
This research has been led by Professor Wolfgang Weninger of the Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia. Weninger worked with other scientists in the U.S., in Australia and in Austria.
The researchers decided to focus on Leishmania because it provokes Leishmaniasis, which "affects up to 12 million people in parts of Africa, the Middle East and South America. The disease causes skin sores and can affect internal organs such as the spleen, liver and bone marrow. If left untreated, it can be fatal."
What is the most important aspect of this research project? Here is Weninger's answer: "We now have a general idea of how pathogens are recognised by the immune system and which cells are involved. This means we can look at identifying the molecules responsible for the uptake of Leishmania infection and these molecules could become vaccine targets. Additionally, we can investigate the immune responses of other infections which could lead to better vaccines."
Centenary Institute Executive Director, Professor Mathew Vadas, says the multi-photon microscope used to film this immune process is the Hubble telescope of medical research. Here is a quote from him. "The Hubble allowed the universe to be seen with absolute clarity, which wasn't before possible from earth. This is exactly the same as multi-photon microscopy - it provides a unique and innovative view of cells, unveiling a whole new understanding of how immune processes work."
This research work has been published by PLoS Pathogens under the -- quite enigmatic -- title "Migratory Dermal Dendritic Cells Act as Rapid Sensors of Protozoan Parasites" (Volume 4, Issue 11, November 2008). Here is a link to this technical article. You can download a PDF version of this paper from this link.
I don't want to put here the long abstract, but here is the author's summary of the article. "Cutaneous Leishmaniasis is a difficult-to-treat disease affecting millions of people worldwide. Hence, there is high demand for the development of vaccines against Leishmania parasites, begging for a better understanding of immune responses against this pathogen. Dendritic cells, as part of the innate immune system, are thought to act as gatekeepers against intruding pathogens. However, their behavior in the context of intact tissues is incompletely understood. Here, we have used intravital two-photon microscopy to visualize the behavior of skin resident dendritic cells in real time, both in the steady-state and upon parasite encounter. We have found that migratory dermal dendritic cells are capable of rapidly sensing Leishmania parasites injected into the skin. This occurred through the formation of highly motile cellular processes capable of engulfing parasites, followed by parasite uptake into the cell. Together, our study provides a new vista of the orchestration of host cell–pathogen encounter in the three-dimensional context of intact tissues. Our results serve as the basis for a better understanding of the dynamic regulation of tissue surveillance by dendritic cells."
Sources: The Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia, December 4, 2008; and various websites
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