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The immune system is the responsible for body integrity and prevention of external invasion. On one side, nanoparticles
are no triggers that the immune system is prepared to detect, on the other side it is known that foreign bodies, not only
bacteria, viruses and parasites, but also inorganic matter, can cause various pathologies such as silicosis, asbestosis or
inflammatory reactions. Therefore, nanoparticles entering the body, after interaction with proteins, will be either
recognized as self-agents or detected by the immune system, encompassing immunostimulation or immunosuppression
responses. The nature of these interactions seems to be dictated not specially by the composition of the material but by
modifications of NP coating (composition, surface charge and structure). Herein, we explore the use of gold
nanoparticles as substrates to carry multifunctional ligands to manipulate the immune system in a controlled manner,
from undetection to immunostimulation. Murine bone marrow macrophages can be activated with artificial nanometric
objects consisting of a gold nanoparticle functionalized with peptides. In the presence of some conjugates, macrophage
proliferation was stopped and pro-inflammatory cytokines were induced. The biochemical type of response depended on
the type of conjugated peptide and was correlated with the degree of ordering in the peptide coating. These findings help
to illustrate the basic requirements involved in medical NP conjugate design to either activate the immune system or hide
from it, in order to reach their targets before being removed by phagocytes. Additionally, it opens up the possibility to
modulate the immune response in order to suppress unwanted responses resulting from autoimmunity, or allergy or to stimulate protective responses against pathogens.
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