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Immune response to Influenza

Seasonal influenza, or the “flu” represents a constant burden to public health, and influenza pandemics caused by new strains pose a serious global threat. Flu and other infections of the throat and lung are often harmless, but sometimes lead to severe tissue damage and in some patients even to death.

Different influenza viruses cause disease of different severity, and when different people are infected by the same virus, the clinical outcome can vary considerably. The immune system is necessary to eliminate the virus, but in the process of doing so the immune response can also cause inadvertent damage to lung tissue. Which factors tip the balance between damage or death in some individuals, versus successful clearance of the virus with no long term damage in others, is not completely understood. Influenza virus infection is also an important risk factor for bacterial superinfections, and both seasonal and pandemic influenza mortality have been associated with pneumonia caused by Streptococcus or Staphylococcus. Therefore, influenza virus also appears to impact on subsequent, unrelated respiratory infections, and the mechanisms of this immune modulatory effect are as yet unclear.

To address these unresolved questions, we investigate viral and host determinants of immunogenicity and pathogenicity in influenza virus infection. A lesson from my previous work on mucosal and parenteral vaccine adjuvants is the crucial importance of early events in the immune response for its successful outcome, which in the case of vaccination is to induce protection. The same parameters are critical for the successful immune response to infection: The way epithelial cells sense infection and transmit this information to immune cells, the local production of chemoattractants and the resulting patterns of immune cell recruitment into the target organ, the degree and quality of immune cell activation, and the functional specialization and cross-talk among innate immune cell subsets. Our aim is to link early events after influenza infection to the final outcome of either virus clearance or damage and death and to the possible induction of an immune compromised state in the lung.

The contribution of these factors is under investigation both in vitro using human and mouse systems of co-culture between airway epithelial and immune cells, and in vivo using murine models of infection and co-infection. These studies are instrumental to understand respiratory viral infections better, to predict their outcome and to identify modes of intervention that enhance protection and prevent damage.

[Page last updated 5 August 2009]

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