Humans can be infected by a plethora of pathogens, including viruses, bacteria and parasites, which cause a wide range of diseases. These so-called infectious diseases are a major cause of morbidity and mortality throughout the world.
For a handful of infectious diseases, such as polio, measles and rubella, the biomedical community has developed effective vaccines that can control the spread of the infection, and in the case of smallpox, essentially eradicate it. For others, such as Human Immundeficiency Virus (HIV), there are effective drugs available that can reduce its impact and substantially prolong patient survival. However, for the majority of infectious diseases we have to rely on our body’s own immune systems to respond and clear the infection.
Ongoing projects at CeMM in the groups of Giulio Superti-Furga, Sylvia Knapp and Andreas Bergthaler are focusing on gaining a better understanding of the immune response to infection, which may enable us to harness its power for treating disease. More specifically during gastrointestinal infections, the group of Clarissa Campbell studies how changes in organismal metabolism impact immune responses.
The innate immune response to infection
Innate immunity is the body’s first line of defence against infection. Many pathogens, particularly viruses, infect human cells in order to propagate. The innate immune response is composed of specialized molecules that have evolved to detect the presence of specific intracellular pathogens and sound the alarm by activating downstream intracellular signalling pathways.
How our immune systems respond to infections is of interest to several groups at CeMM.
- Giulio Superti-Furga’s group use systems biology approaches including proteomics to gain a comprehensive understanding of the signalling networks underlying the innate immune response to infection. The discovery of AIM2 as a DNA-recognizing moiety of the inflammasome and of the IFIT proteins as nucleic acid recognizing anti-viral effectors count among CeMM’s most important achievements thus far.
The innate immune system's response to invading pathogens serves to limit the systemic spread of the infection and to minimize tissue damage and the resulting organ failure.
- Sylvia Knapp’s group uses a resourceful approach to study the intricate interaction between pathogens and host structures to understand and identify novel ways to improve host defense and tolerance towards bacterial infections. As such, Sylvia Knapp´s group recently discovered how hemolysis predisposes to bacterial infections and developed a novel immunodadjuvant approach to prevent the detrimental effects of hemolysis.
Interplay between persistent viruses & the host immune system
Persistent viral infections, which affect millions of people worldwide.
- Andreas Bergthaler’s group is interested in both the innate and the adaptive immune response to persistent viral infections. They use genetics approaches and a prototypic infection model with a small mouse virus to study how the virus interacts with the innate immune system as well as with CD8 T and B cells. They also study how certain chronic viral infections can effectively suppress the immune system, which can leave the body open to so-called superinfections by bacteria or other viruses.
Infection is often accompanied by metabolic and behavioral alterations including fever, anhedonia and anorexia. Reduced feeding during infection decreases splenic lymphocyte numbers, suggesting the existence of metabolic states that better support immune function. Despite the well-characterized role of pleiotropic inflammatory cytokines in promoting sickness behavior, the effects of challenge-specific mediators on organismal physiology remain poorly characterized. Intestinal helminthic infections induce strong type 2 immune responses associated with a 10% increase in the resting metabolic rates of infected individuals in non-industrialized countries. The consequences of such metabolic shifts on immunity remain unknown.
- Clarissa Campbell's group at CeMM uses transcriptional profiling and mouse genetic models to dissect the molecular pathways mediating organismal metabolic adaptation during helminthic infection with the goal of understanding how these changes impact the immunological balance at the intestinal mucosa.