Targeting Immune Cells.

Abstract

The respiratory tract with its vast surface area and very thin air-blood tissue barrier presents an extremely large interface for potential interaction with xenobiotics such as inhaled pathogens or medicaments. To protect its large and vulnerable surface, the lung is populated with several different types of immune cells. Pulmonary epithelial cells, macrophages and dendritic cells are key players in shaping the innate and adaptive immune response. Due to their localization, they represent a frontline of cell populations that are among the first to come in contact with inhaled xenobiotics. Furthermore, depending on the lung compartment they populate, these cells show a large variety in morphology, phenotype, and function. These unique characteristics make those cell populations ideal targets for specific immunomodulators that are designed for inhalation. Depending on cell population or lung compartment targeting, a specific immune response may be triggered or modulated. The purpose of a potent carrier for pulmonary immunomodulation is, first, to efficiently target a specific immunocompetent cell and, second, to affect its role in generating an immune response. Immunomodulation may occur at different levels of immune cell-antigen interaction, i.e. antigen uptake, trafficking, processing and presentation. Inhalation of nanosized carriers for drugs or vaccines shows great potential for both prophylactic and therapeutic approaches in order to modulate immune responses locally or systemically, due to the specific deposition and targeting properties of nanoparticles. Immune responses triggered by nanosized particles may be either immunostimulatory or immunosuppressive and depending on the specific purpose, stimulation or suppression may either be desired or unwanted. Meticulous analysis of immunomodulatory potential, pharmacologic and toxicologic testing of inhalable nanocarriers is required in order to find novel and optimal approaches for prophylaxis and therapy of pulmonary diseases. The design and characterization of such nanoparticles requires well-coordinated interdisciplinary research among engineers, biologists and clinicians.