Immune Aging and Chronic Infections

“Back then, I wasn’t ill so often”: With advancing age not only the skin loses its elasticity – many organs lose their functions. So does the immune system: Defense cells do not react promptly anymore, and immunological memory is not established. As a result, we are poorly protected by vaccines and more susceptible to infections, but at the same time suffer from inflammatory disease. While the mechanisms of immune aging remain unknown, chronic viral infections are environmental factors that may accelerate the age-related changes of the immune system. Read more about how pathogens may have an impact on the real age of our immune system.

Leader

Our Research

The scientists from the research group “Immune aging and chronic infections” study ubiquitous viruses that are persist for life in most people worldwide. In particular, our focus is on herpesviruses, whose persistence during latent infection shapes the immune system and its functionality.

Cytomegalovirus (CMV) is a herpes virus that is latently maintained in the vast majority of the human population worldwide. Epidemiological studies in otherwise healthy individuals showed that immune responses to CMV dominate the memory compartment of CMV seropositive people. It follows that immunological memory to CMV infection dominates the memory compartment of most adult people around the globe. It is unclear why this single virus commands such a strong attention of our immune system, but virus persistence seems to play a prominent role in this phenotype. Regardless of its causes, it is speculated that the huge footprint of the CMV infection on the immune system may drive chronic inflammatory conditions that contribute to the dysfunctions associated with aging. Finally, even if this was wrong, even if the strong immunity to CMV had no consequences whatsoever on our well-being, the uniquely strong immunity to this virus remains a highly interesting phenomenon, because it can provide us clues on how to develop better and more efficient vaccines.

The research group "Immune aging and Chronic Infections" is developing novel models of life-long CMV infection in animal models, to match the clinical observations and define the consequences of a life-long CMV latency. Furthermore, we have developed novel reporter assays to monitor the virus infection process at the single cell level and identify viral gene expression in presence of immune cells. Taken together, our technologies allow us to model the productive and the latent infection in the presence of immune cell populations, understand why CMV reactivates in immunocompromised patients and develop new antiviral strategies.

The researchers propose to address two major aims in this unique model:

  1. define the cellular and molecular mechanisms underlying the strong immune response after CMV infection, and
  2. assess the broader biological relevance of the robust immunity to CMV and other persistent viruses, by testing if they contribute to chronic inflammatory diseases or decrease immune protection against emerging infections.


Given the ubiquitous presence of CMV, and the aging demographic trend in developed countries, the results of this project are likely to have high medical and social impact. Understanding the mechanisms that delay immune senescence may give us preventive and therapeutic tools to improve significantly the quality of life of seniors, an increasingly important task in an aging society. Chronic infections seem a smart target to avert immune senescence.

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