(545a) Shape-Dependent Modulation of Immune Response to Pathogens

The immune system has evolved remarkably to recognize and respond to a wide variety of pathogens and produce distinct immune responses against diverse pathogenic structures. Despite remarkable immunological advancements, the generalized mechanism by which the immune system differentiates distinct pathogens is yet to be elucidated. This is due to vast variations in physical (for example, size, shape, surface charge, functional groups, and hydrophobicity) and chemical (for example, surface antigen) properties of pathogens. In particular, pathogen shape has gained wide attention in recent years for its ability to influence pathogen interaction with key components of the immune system, such as macrophages, dendritic cells, complement proteins and T-cells. However, the significance of pathogen shape in immune response modulation is not yet explored. This is primarily due to the limited availability of safe pathogens, which display similar physicochemical properties, but varying shapes. Moreover, it is technically quite challenging to modify the shapes of biological disease-causing pathogens. A potential solution to these limitations includes the use of safe, non-biological pathogen mimicking structures, which mimic pathogen induced immune responses without the associated adverse effects of a pathogen. To address this issue, we report herein the importance of shapes in mimicking pathogenic structures and their role in modulating the immune response. In the current study, we report hydrophobic polystyrene particles of various sizes and shapes, displaying a model antigen (ovalbumin) on their surface, as pathogen-mimicking structures, and evaluated their role in generating distinct shape-dependent immune responses against the antigen. The results revealed that spherical (200 nm in diameter) particles produced a Th1-biased (cellular) immune response that is characteristic of viruses and rod-shaped (1500 nm in length) particles produced a Th2-biased (humoral) immune response that is characteristic of bacterias. Among different pathogenic structures, smaller spherical particles (200 nm in diameter) produced stronger immune response as compared to larger spherical (500 nm in diameter) or rod-shaped (450 nm and 1500 nm in length) particles. These results provide evidence of shape-dependent modulation of immune system against diverse pathogenic structures. This knowledge can be used to rationally design “pathogen-mimicking” materials and develop next generation vaccines that can induce appropriate immune responses to protect against a wide range of pathogens.