It takes two to tango: Understanding the interactions between engineered nanomaterials and the immune system

• Engineered nanomaterials possess both a synthetic and a biological “identity”.
• The bio-corona may dictate how nanomaterials interact with the immune system.
• Inflammasome activation has been documented for several different nanomaterials.
• Interactions between nanomaterials and the innate immune system may be reciprocal.

The immune system represents our primary defense system against foreign intrusion, including pathogens as well as particles. In order to understand the potential toxicity of engineered nanomaterials of ever increasing sophistication, it is necessary to understand the sophistication of the immune system with its multiple, specialized cell types and soluble mediators. Moreover, it is important to consider not only material-intrinsic properties of the pristine nanomaterial, but also the acquired, context-dependent ‘identity’ of a nanomaterial in a living system resulting from the adsorption of biomolecules on its surface. The immune system has evolved to recognize a vast array of microbes through so-called pattern recognition; we discuss in the present review whether engineered nanomaterials with or without a corona of biomolecules could also be sensed as ‘pathogens’ by immune-competent cells.

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