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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.

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.

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"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 story is based on 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 March 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 March 4, 2015).

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