Innate immunity plays a central role in protection during virus infection of the respiratory tract and in regulating the generation of adaptive immune responses. Dendritic cells are a critical component of the innate immune system, yet little is known about their interplay with other components of the ongoing immune response in the lung. This is of special relevance because the respiratory tract is the main portal of microorganism entry in the body, and respiratory infections constitute the leading cause of illnesses worldwide, being responsible for 4 million deaths/year. The overall objective of this project is to elucidate how dendritic cells and the lung microenvironment interact during the priming and recall of T cell responses to respiratory pathogens. The concept that virus-induced epithelial signals determine dendritic cell education in the lung, and ultimately the quality of the local adaptive immune response is novel, and constitutes the foundation of this proposal. We build on our previous studies and explore three fundamental questions: (1) What is the role of type I interferon signaling in the epithelium-dendritic cell interplay in the respiratory tract? (2) What is the role of pathogen recognition receptors on the recruitment of T cells into the respiratory tract? (3) What is the contribution of pulmonary dendritic cells to the recall of local memory responses in the lung mucosa?
Acute respiratory viral infections are one of the leading causes of acute illnesses around the world. The lung is the major portal of entry of many devastating human pathogens including respiratory viruses such as influenza. However, we only have a poor understanding of the mechanisms by which dendritic cells in the respiratory tract induce and regulate adaptive immune responses during infection. A detailed understanding of the molecular and cellular innate mechanisms that regulate anti-viral adaptive responses in the lung will be essential for the future design of therapies to control infection and to prevent undesired inflammation.
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