The rise in use of nanotechnology has significantly increased risks of human exposure and interaction of nanoparticles with the immune system, potentially jeopardizing host responses to infection. There is a critical need to define the functional immunological consequences of chronic nanoparticle exposure. Lack of this knowledge could potentially confound efforts to prevent, diagnose, and treat infectious diseases in people whose immune system responses may have been affected by exposure to nanomaterials. The objective of the proposed studies is to define genetic and innate immune responses of zebrafish neutrophils to exposure to nano-TiO2 as well as functional consequences in host responses to disease causing pathogens. The hypothesis is that exposure to nano-TiO2 will 1) cause measurable changes in leukocyte transcriptome response and neutrophil function; and 2) increase morbidity and mortality in disease challenged zebrafish. The rationale for the proposed research is that insights into nano-TiO2 dependent changes in host immune response to pathogens will allow better assessment of risks associated with chronic exposures to metallic oxide nanoparticles.The public health relevance of the proposed research is reflected in the fact that nano products are rapidly accumulating in the environment and their potential for causing adverse health effects is growing proportionately, but the contribution of environmentally-relevant nanoparticle doses to modulation of infectious disease pathology remains unclear. The proposed research is significant because it is expected to increase our mechanistic understanding of the biological activity of nano-metallic oxides and assess their potential for chronic toxicity, and to allow us to evaluate the safety of metallic oxide nanoparticles. Integration of Dr Palic to EU scientific community network will be greatly enhanced with this opportunity to retain and expand collaborations with knowledge transfer from the U.S. to Germany.