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New defense mechanism against viruses and cancer identified

Date:
February 15, 2012
Source:
Deutsches Rheuma-Forschungszentrum Berlin
Summary:
Scientists have found a fundamentally new mechanism how our defense system is ramped up when facing a viral intruder. Exploitation of this mechanism in vaccines sparks new hope for better prevention and therapy of infectious diseases and cancer.
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Fundamentally new mechanism of how our defense system is ramped up when facing a viral intruder.
Credit: Image courtesy of Deutsches Rheuma-Forschungszentrum Berlin

A team of scientists from the Charité and German Rheumatism Research Center Berlin and the University of Geneva has found a fundamentally new mechanism how our defense system is ramped up when facing a viral intruder. Exploitation of this mechanism in vaccines sparks new hope for better prevention and therapy of infectious diseases and cancer.

"T killer cells" (CD8 T cells) represent an important element of our body's defense system. They have the capacity to specifically identify and kill cells, which harbor viruses and bacteria or form a cancer. T killer cells would therefore represent an important component of yet unavailable vaccines against infections like HIV/AIDS, hepatitis C virus and malaria, and also for the treatment of cancer.

It has been a longstanding observation that there is no match to the overwhelming T killer cell armada, which is triggered when a viral infection invades our body. Scientists had generally accredited this observation to "pathogen-associated molecular patterns" (PAMPs) on viruses and other microbes. PAMPs, i.e. the "foreign look" of viruses, alert so-called "dendritic cells," which serve as policemen coordinating the T killer cell response.

In a report now published in the journal Science, researchers led by Prof. Max Löhning (Charité-University Medicine & DRFZ Berlin) and Prof. Daniel Pinschewer (University of Geneva) describe an additional general mechanism by which viral infection triggers potent T killer cells: "Dying virus-infected cells themselves ring the alarm bells to T killer cells.," Löhning says. Viruses cause infected cells to die, resulting in the release of cell components, which normally are not be visible to the outside -- analogous to an injured individual loosing blood. Such substances, heralding injury when released, are referred to as "alarmins." The scientists found that T killer cells can sense an alarmin called "interleukin 33" (IL-33). IL-33 is contained in cells, which form the scaffold of the T killer cells' home, the spleen and lymph nodes, and is released when such scaffold cells die.

Mice lacking the gene encoding IL-33 failed to form a large T killer cell army upon viral infection. The few remaining cells had very poor fighting skills. Such mice were therefore exquisitely sensitive to several types of viral infections. Conversely, IL-33 could be used to artificially increase the T killer cell army, which was generated in response to vaccination. As Max Löhning and Daniel Pinschewer explain, PAMPs and alarmins apparently have complementary and non-redundant functions in shaping our T killer cell defense: "The "foreign look" of viruses (PAMPs) activates the "dendritic cell" policemen to engage T killer cells. T killer cells, however, remain lousy fighters unless alerted by a cell death in their neighborhood (alarmins)." These new findings could provide a key to effective vaccination against infectious diseases and cancer.


Story Source:

The above post is reprinted from materials provided by Deutsches Rheuma-Forschungszentrum Berlin. Note: Materials may be edited for content and length.


Journal Reference:

  1. W. V. Bonilla, A. Frohlich, K. Senn, S. Kallert, M. Fernandez, S. Johnson, M. Kreutzfeldt, A. N. Hegazy, C. Schrick, P. G. Fallon, R. Klemenz, S. Nakae, H. Adler, D. Merkler, M. Lohning, D. D. Pinschewer. The Alarmin Interleukin-33 Drives Protective Antiviral CD8 T Cell Responses. Science, 2012; DOI: 10.1126/science.1215418

Cite This Page:

Deutsches Rheuma-Forschungszentrum Berlin. "New defense mechanism against viruses and cancer identified." ScienceDaily. ScienceDaily, 15 February 2012. <www.sciencedaily.com/releases/2012/02/120215123702.htm>.
Deutsches Rheuma-Forschungszentrum Berlin. (2012, February 15). New defense mechanism against viruses and cancer identified. ScienceDaily. Retrieved July 4, 2015 from www.sciencedaily.com/releases/2012/02/120215123702.htm
Deutsches Rheuma-Forschungszentrum Berlin. "New defense mechanism against viruses and cancer identified." ScienceDaily. www.sciencedaily.com/releases/2012/02/120215123702.htm (accessed July 4, 2015).

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